ScienceWeek

SCIENCE-WEEK

A Weekly Email Digest of the News of Science

A journal devoted to the improvement of communication
between the scientific disciplines, and between scientists,
science educators, and science policy-makers.

October 12, 2001 -- Vol. 5 Number 41

-----------------------------------------------

Between the fifth and tenth days the lump of stem cells
differentiates into the overall building plan of the
mouse embryo and its organs. It is a bit like a lump
of iron turning into the space shuttle. In fact it is
the profoundest wonder we can still imagine and accept,
and at the same time so usual that we have to force
ourselves to wonder about the wondrousness of this wonder.
-- Miroslav Holub

-----------------------------------------------

=-=-=-=-=-=-=-=-=
Section 1
=-=-=-=-=-=-=-=-=

Contents of this Issue (Full reports in Section 2):

1. History of Physics: Thomas Hariot (1560-1621)
2. Climate Change on Venus
3. Quantum Physics: Dynamical Tunneling
4. Studies of Dendrimers
5. Preparation of Carbon Nanotubes
6. Simulations of Phospholipid Bilayer Formation
7. On Reorganization in the Cerebral Cortex
8. Computer Models of Invertebrate Segmentation
9. Mismatch-Repair Genes and Genomic Stability
10. Alzheimer's Disease and Secretases
11. Glutamate and Neurological Disease
12. Developmental Potential of Cloned Mammalian Embryos
13. In Focus: On the Copernican Revolution
14. SW Archive: On Philosophical Extrapolations in Physics
15. Sources

=-=-=-=-=-=-=-=-=
Section 2
=-=-=-=-=-=-=-=-=

1. HISTORY OF PHYSICS: THOMAS HARIOT (1560-1621)
Hans C. von Baeyer (College of William & Mary, US) discusses
Thomas Hariot (Harriot) (1560-1621). Hariot was a mathematician,
deriving fundamental theorems in cartography, trigonometry and
algebra, and adding the symbols > and < to the mathematical
lexicon. He worked on mirrors and lenses, and built telescopes
contemporaneously with Galileo. With these telescopes, Hariot
independently discovered the phases of Venus, made the first map
of the Moon, and anticipated Galileo in observing sunspots and
measuring the periods of the satellites of Jupiter. His
observations of the comet of 1607, the comet later to become
famous as "Halley's comet", were good enough to be used in
cometary orbital calculations 200 years later. Among Hariot's
wide-ranging interests was the phenomenon of refraction. During
Hariot's time, the laws of refraction were eagerly sought by the
designers of optical instruments as well as by astronomers who
wanted to correct for the effect of Earth's atmosphere on
starlight. The inherited lists and rules of thumb for describing
refraction were known to be incomplete and in places highly
inaccurate. Unlike the eminent astronomer Johannes Kepler (1571-
1630), who disdained painstaking experimentation and relied
instead on various approximate formulae arrived at by
speculation, Hariot perfected a simple technique for observing
refraction, and with this technique he discovered the correct law
of refraction by 1602, 19 years before Willebrord Snell (1580-
1626), who is usually given credit for the discovery.
-----------
NS 2001 11 Aug
-----------
SCIENCE-WEEK 12 Oct 2001 http://scienceweek.com
-------------------
Related Background:
VERIFICATION OF NEGATIVE REFRACTIVE INDEX MATERIALS
     In physics, the term "refraction" refers to the change in
direction of a wave passing from one medium to another, the
change occurring when the wave velocity differs in the two media.
Given the velocity-difference condition, there is only one
instance when there is no change in wave direction, and that is
when the incidence of the wave is exactly perpendicular to the
interface between the media. The phenomenon of refraction is
exhibited by any wave, including light waves, sound waves, water
waves, etc., and the major quantitative details were worked out
in 1621 by Willebrord Snell (1580-1626). The electromagnetic
waves that constitute light are thus refracted when crossing the
boundary from one transparent medium to another, if the wave
velocities in the two media differ and the incident light strikes
the interface at an angle different from the perpendicular. But
all waves in the electromagnetic spectrum can exhibit refraction,
including all waves from the shortest waves to waves in the
microwave and radio region.
     In this context, the term "refractive index" (refractive
constant) takes two forms: a) The "absolute refractive index" of
a medium is the ratio of the velocity of electromagnetic
radiation in free space to the velocity of the radiation in the
medium. b) The "relative refractive index" is the ratio of the
velocity of electromagnetic radiation in one medium to that in an
adjacent medium. In general, the refractive index varies with
wavelength, and the usual method is to standardize by denoting
the refractive index as related to the wavelength of the sodium D
line.
... ... R.A. Shelby et al (3 authors at University of California
San Diego, US) present a report of an experimental verification
of a negative index of refraction, the authors making the
following points:
     1) The authors point out that refraction is perhaps one of
the most basic of electromagnetic phenomena, whereby when a beam
of radiation is incident on an interface between two materials at
an arbitrary angle, the direction of propagation of the
transmitted beam is altered by an amount related to the indices
of refraction of the two materials. Snell's law, arrived at by
requiring that the phase of the incident and transmitted beams be
the same everywhere at the interface, provides the quantitative
relation between the incident and refractive angles (the angles
measured from the refraction interface normal) and the indices of
refraction of the media. The law takes the form
(a)sin(A) = (b)sin(B), where (a) and (b) are the refractive
indices of media 1 and 2, respectively, and (A) and (B) are the
refractive angles in media 1 and 2, respectively. A refracted ray
is thus bent toward the normal (but never emerges on the same
side of the normal as the incident rays) upon entering a
naturally occurring material from air, as most materials have an
index of refraction greater than 1.
     2) The authors point out that refraction forms the basis of
lenses and imaging, as any finite section of material with a
refractive index differing from that of its environment will
alter the direction of incoming rays that are not normal to the
interface. Lenses can thus be designed to focus and steer
radiation for a wide range of applications and are of use over a
large range of wavelengths. Although all known naturally
occurring materials exhibit positive indices of refraction, the
possibility of materials with negative refractive index has been
explored theoretically, and the conclusion has been that such
materials would not violate any fundamental physical laws.
     3) The authors report experimental scattering data at
microwave frequencies on a structured metamaterial that exhibits
a frequency band where the effective index of refraction is
negative. The material consists of a 2-dimensional array of
repeated unit cells of copper strips and split ring resonators on
interlocking strips of standard circuit board material. By
measuring the scattering angle of the transmitted beam through a
prism fabricated from this material, the authors determined the
effective refractive index appropriate to Snell's law. The
authors suggest their experiments directly confirm the
predictions of Maxwell's equations that the refractive index is
given by the negative square root of the product of *permittivity
and *permeability for the frequencies where both the permittivity
and permeability are negative.
     4) The authors conclude: "The use of *photonic crystals as
negative refractive materials is intriguing and may offer the
means of extending the phenomenon we report here to optical
wavelengths. Any material that exhibits the property of negative
refractive index, a property not observed in naturally occurring
materials, will have a variety of practical applications, such as
beam steerers, modulators, band-pass filters, and lenses
permitting wavelength point source focusing."
-----------
R.A. Shelby et al: Experimental verification of a negative index
of refraction.
(Science 6 Apr 01 292:77)
QY: R.A. Shelby: Department of Physics, University of California
San Diego, La Jolla, CA 92093-0350 (US).
-----------
Text Notes:
... ... *permittivity: In general, in this context, the term
"permittivity" (dielectric constant) refers to the ratio of the
electric displacement in a medium to the intensity of the
electric field producing the displacement.
... ... *permeability: In general, in this context, the term
"permeability" refers to the ratio, in a substance, of the
magnetic flux density to the external magnetic field strength.
The relative permeability of a substance is given by the ratio of
the permeability of the substance to the permeability of free
space.
... ... *photonic crystals: In general, "photonic crystals" are
crystals with a lattice that diffracts visible light. Since the
wavelength of visible light is much longer than the wavelength of
x-rays, in order for diffraction of visible light to occur, the
distances between atoms in a photonic crystal must be much
greater than in an ordinary crystal.
-----------
SW 2001 4 May
-----------
SCIENCE-WEEK 12 Oct 2001 http://scienceweek.com

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

2. CLIMATE CHANGE ON VENUS
Ronald G. Prinn (Massachusetts Institute of Technology, US)
discusses the climate of Venus. The average surface temperature
of Venus is 735 kelvins, approximately 435 kelvins higher than
that of Earth. Venus has a thick atmosphere of carbon dioxide
that exerts a surface pressure approximately 92 times greater
than Earth's. The craters and volcanoes of Venus are completely
shrouded by thick clouds of sulfuric acid and its surface
features are revealed only in radar images. Venus has no oceans
and no known life. An important question concerning Venus is how
stable is its climate? A new report by M. Bullock and D.
Greenspoon (2001) describes a simulation of the climate of Venus
that suggests the Venusian climate has oscillated over the past
billion years between periods of global cooling and global
warming. The simulation involves a new radiative-convective model
of the Venusian climate, and is based on recent data from
spacecraft and from ground-based telescopes, which together
provide information on the geology, geophysics, and atmospheric
chemistry of Venus. The model also includes data on the rates of
reaction of these gases with surface minerals at high
temperatures, and the climate model is coupled to models of cloud
microphysics, volcanic outgassing of sulfur dioxide and water
from the crust, surface chemistry, and water loss due to hydrogen
atoms escaping from the high atmosphere into space. The Bullock-
Greenspoon model is the first to use high-temperature high-
resolution spectroscopic data on the absorption properties of the
major greenhouse gases found on Venus (mainly carbon dioxide with
trace amounts of water and sulfur dioxide). The model indicates
that between 600 million and 1100 million years ago, Venus was
cooler than it is today.
-----------
NAT 2001 412:36
Icarus 2001 150:19
-----------
SCIENCE-WEEK 12 Oct 2001 http://scienceweek.com
-------------------
Related Background:
ON THE GEOLOGICAL EVOLUTION OF VENUS
Seismic studies indicate the interior of the Earth consists of
three parts: a hot metallic core, a dense rocky mantle, and a
thin low-density crust. The central part of the core is solid,
but the outer part of the core is evidently liquid. In geology, a
"dome" is a circular or elliptical upfold type of structural
deformation; a "rise" is a long and broad elevation rising gently
from its surroundings; "mantle plumes" are thin vertical conduits
of molten rock material from the core-mantle boundary to the
crust. The term "lithosphere" refers to the outer layer of the
Earth, comprising the crust and upper mantle, and extending to a
depth of 50 to 70 kilometers. All of these terms have
applications in the study of the geology of other planets.
... ... Phillips and Hansen (2 installations, US) review extant
data concerning the geology of crustal plateaus and volcanic
rises on Venus, and present a model for their formation, and a
model of the thermal evolution of the lithosphere of Venus. The
authors suggest that crustal plateaus and volcanic rises on Venus
formed as a result of the interaction with the lithosphere of
mantle plumes rising from the core-mantle boundary, and that the
climate and internal history of Venus were strongly coupled
throughout much of its history.
-----------
SCI 1998 6 Mar
SW 1998 20 Mar
-----------
SCIENCE-WEEK 12 Oct 2001 http://scienceweek.com

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

3. QUANTUM PHYSICS: DYNAMICAL TUNNELING
W.K. Hensinger et al (National Institute of Standards and
Technology, US) discusses dynamical tunneling. The divergence of
quantum and classical descriptions of particle motion is clearly
apparent in quantum tunneling between two regions of classically
stable motion. An archetype of such nonclassical motion is
tunneling through an energy barrier. In the 1980s, a new process,
"dynamical tunneling", was predicted, this process involving no
potential energy barrier, but involves a constant of the motion
(other than energy) allowing a quantum motion that is forbidden
classically. This process should occur, for example, in
periodically driven nonlinear hamiltonian systems with one degree
of freedom. Such systems may be chaotic, consisting of regions in
phase space of stable and regular motion embedded in a sea of
chaos, and previous studies predicted dynamical tunneling between
these stable regions. The authors report the observation of
dynamical tunneling of ultracold atoms from a Bose-Einstein
condensate in an amplitude-modulated standing wave. Atoms
coherently tunnel back and forth between their initial state of
oscillatory motion (corresponding to an island of regular motion)
and the state oscillating 180 degrees out of phase with the
initial state. In a commentary on this work, Eric J. Heller
(Harvard University, US) notes: "These and other recent
experiments demonstrate that it is possible to exert quantum
control over ultracold atoms with astonishing finesse and
coherence."
-----------
NAT 2001 412:33,52
-----------
SCIENCE-WEEK 12 Oct 2001 http://scienceweek.com
-------------------
Related Background:
DYNAMICAL TUNNELING
Barbara Goss Levi (Physics Today) discusses dynamic tunneling of
atoms. It has been long understood that atoms in a double
potential well can move back and forth between wells, even though
classically an atom with insufficient energy is precluded from
surmounting the energy barrier between the two compartments.
Thus, it not surprising to learn that an atom executing one type
of regular motion can suddenly be found to be moving 180 degrees
out of phase with its initial motion, i.e., moving in the
opposite direction. That is the idea behind "dynamic tunneling",
or the hopping of particles between separate and stable regions
in phase space. Although there has been some evidence for
dynamical tunneling in molecular systems, it has now been
observed very directly in new experiments on ultracold atoms. In
general, dynamical tunneling involves a system phase space in
which two modes are separated not by an energy barrier but by a
barrier in some other variable of the system. The transition from
one mode to another was termed "dynamical tunneling" by Heller
and Davis in 1981. One example of dynamical tunneling is a
rotating molecule like formaldehyde. This molecule can flip
between two states, with the line from the carbon to the oxygen
atom either parallel or antiparallel to the molecule's angular
momentum vector. One cannot directly photograph the molecule
flipping between these two states, but one can infer that such
flipping occurs from the splitting of the rotational energy
levels. Dynamical tunneling splits the energy levels just as
tunneling through an energy barrier splits the energy levels of a
particle in a potential well.
-----------
PT 2001 August
SW 7 Sep 2001
-----------
SCIENCE-WEEK 12 Oct 2001 http://scienceweek.com

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

4. STUDIES OF DENDRIMERS
J.D. Epperson et al (University of South Florida, US) discuss
studies of dendrimer structure. Dendrimers are highly branched
macromolecules with "tree-like" structures and are synthesized by
repetitively linking molecular building blocks AB(subn), with (n)
usually 2 or 3, to a central core. Since both the internal and
external chemical functionalities of dendrimers can be tailored
to alter their physical and chemical properties, several
potential applications are recognized for these polymers,
including catalysis, self-assembly, and molecular recognition and
encapsulation. For example, the incorporation of 2,6-
diamidopyridino H-bonding sites into internal regions of a
polyamido dendrimer facilitates the selective encapsulation of
"guest" molecules such as barbituric acid and azidothymidine
(AZT) into the interior of the dendrimer. Moreover, modification
of the dendritic exterior is being explored to produce dendrimers
for chromatography additives, antibody conjugates, gene therapy,
and electrically conducting materials. The possibility of
entrapping small molecules inside host dendrimers has raised
great interest in the structural and chemical characterization of
these unique macromolecules. However, detailed structural
analysis of dendrimers by means of x-ray crystallography and NMR
spectroscopy have been hindered by the size and fractal nature of
these molecules. 
-----------
JACS 2001 123:8583
-----------
SCIENCE-WEEK 12 Oct 2001 http://scienceweek.com

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

5. PREPARATION OF CARBON NANOTUBES
M. Motiei et al (Bar-Ilan University, IL) discuss methods for
preparing nanotubes. The discovery of carbon nanotubes in 1991 by
S. Iijima has led to extensive research due to the unique
properties of these systems. Carbon nanotubes have potential
applications as superconductors, single-molecule transistors, and
(when the nanotube is filled with metals or metal oxides) as part
of magnetic recording devices. The various methods of preparing
carbon nanotubes can be classified into two categories: physical
methods and chemical methods. The physical techniques are
characterized by low nanotube yield, technical complexity, and a
very low energetic efficiency that makes them unsuitable for mass
production. These methods include electric arc synthesis, laser
ablation, resistivity vaporization, electron or ion beam
vaporization, and sunlight-induced vaporization. In contrast, the
chemical methods are aimed at mass production with reasonable
yields and low energy consumption. However, the chemical methods
usually result in nanotubes of lower quality. The chemical
reactions employed include the catalytic pyrolysis of
hydrocarbons, catalytic disproportionation of carbon monoxide,
the reduction of perfluorinated hydrocarbons by an alkali metal
amalgam, hydrothermal growth from amorphous carbons, the
catalytic reduction of carbon monoxide, oxidation of
C(sub2)H(sub2), polymerization of C(sub6)H(sub2), a metathesis
reaction, and the thermal decomposition of Fe[CO](sub5) in a
heated flow of carbon monoxide.
-----------
JACS 2001 123:8624
-----------
SCIENCE-WEEK 12 Oct 2001 http://scienceweek.com

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

6. SIMULATIONS OF PHOSPHOLIPID BILAYER FORMATION
S.J. Marrink et al (University of Groningen, NL) discuss
phospholipid bilayers. The self-aggregation of lipid molecules to
form bilayer membranes is a process fundamental to the
organization of life. Although qualitatively explained by the
hydrophobic effect, the molecular aggregation itself is a complex
phenomenon that has not been possible to study in detail
experimentally. The authors report a series of molecular dynamics
computer simulations that for the first time demonstrate the
possibility of observing the entire process at atomic resolution
with realistic lipids. Starting from random solutions, bilayers
are formed on time-scales of 10 to 100 nanoseconds, with
properties matching experimental data. Several key steps and
approximate time scales of the aggregation can be identified. The
final rate-limiting process is the reduction and disappearance of
large hydrophilic transmembrane water pores, which is of
biological relevance, e.g., for ion permeation. S.J. Singer and
G.L. Nicholson (1972) were the first to recognize the
implications of the extreme flexibility of membranes for the
structure of cellular walls, leading to the famous "fluid-mosaic
model" with diffusing lipids and proteins. However, the bilayer
formation process is extremely fast and involves subtle
rearrangements at the molecular level, making it elusive for
current experimental methods. The authors suggest their work
demonstrates the first simulations of aggregation of lipids into
bilayers with atomic resolution of the structure and
interactions.
-----------
JACS 2001 123:8638
-----------
SCIENCE-WEEK 12 Oct 2001 http://scienceweek.com

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

7. ON REORGANIZATION IN THE CEREBRAL CORTEX
T. Elbert and S. Helm (University of Konstanz, DE) discuss
reorganization in the cerebral cortex. The gigantic network that
makes up the human cerebral cortex is dynamically and unceasingly
reorganizing itself. This continuously changing entity is not
easy to track, but the living brain can be glimpsed by observing
the organization within zones representing the first stages of
sensory input from the outside world. Primary auditory, visual,
and somatosensory cortices mirror the spatial arrangement of the
respective peripheral receptors: tonal frequency (place in the
cochlea), visual space (place on the retina), or body surface are
represented in the form of maps imprinted on the cortical sheet.
Although genetically encoded programs control the connections of
these maps from the periphery to the cortical destination, their
organization ultimately depends on the efficacy of the synapses
connecting the nerve cells comprising the network, which efficacy
in turn is affected by environmental experience. Another
important consideration is that the functional organization of
one level of the cortex is governed by the interplay of earlier
and later representational stages of the sensory processing
stream. In mammals, the thalamus (one of the highest processing
stages of the reptilian brain) feeds sensory information into the
cortex. The cortex in turn feeds processed information back to
the thalamus. When these top-down projections are inactivated,
thalamic functional organization is dramatically degraded.
Furthermore, in a nonlinear dynamic self-organizing system such
as the brain, small causes can have large effects. The brain
should not be studied only in terms of monocausal genetic and
environmental influences. Learning consists of the adaptation of
brain dynamics.
-----------
NAT 2001 411:139
-----------
SCIENCE-WEEK 12 Oct 2001 http://scienceweek.com
-------------------
Related Background:
ON BRAIN PLASTICITY AND STROKE
In human brain research, the term "plasticity" refers to the
ability of various regions of the brain to assume specific
functions as the result of experience, and also the ability of
various regions of the brain to assume the functions of other
regions that are damaged by disease or trauma ("adaptive
plasticity"). Important questions concerning the biological basis
of plasticity are a) What are the neural mechanisms responsible
for plasticity? and b) What are the conditions which limit
plasticity? Until recently, the primary source of evidence in
this field was "anecdotal" -- evidence from individual clinical
cases. That has changed: during the past decade, numerous studies
have been carried out using non-invasive methods to monitor
ongoing localized brain activity in conscious subjects, and
evidence concerning plasticity and other characteristics of human
brain function is rapidly mounting.
... ... N.P. Azari and R.J. Seitz (Heinrich Heine University, DE)
present a review of current research in brain plasticity and
recovery from stroke, the authors making the following points:
     1) When a particular neural network is damaged, as often
happens in a stroke, the system fails and function is initially
lost because no other neurons in the brain are "wired" to do the
task formerly performed by the damaged network. The result may be
paralysis or the loss of speech or the inability to comprehend
speech or any one of a number of actions. But many people who
have suffered a stroke regain some or most of the lost functions
after a brief recovery period, sometimes in a matter of weeks.
     2) The capacity of the brain to reorganize itself -- its
"plasticity" -- in the process of learning a task is perhaps the
most interesting phenomenon that distinguishes the nervous system
from all other tissues in the body. The plasticity of the brain
appears to be greatest when we are young (from infancy through
early adolescence), a time when many of the neural pathways that
will be used for the acquisition of language and motor skills are
formed. But our ability to learn new languages and new skills as
adults indicates that the brain retains a certain level of
plasticity throughout our lives (although our potential for
learning new languages and skills may be decreased).
     3) Many studies have shown that stroke patients require time
to regain function. During this time, the brain is evidently
sorting out how it might compensate for the damaged neurons, and
the subsequent process of neural recovery appears to occur in
several stages:
... ... a) Initially there is a passive tissue response in the
first few hours and days following brain-tissue injury. This
passive response involves the reperfusion of tissue deprived of
blood-oxygen (ischemic tissue) and cessation of *inflammatory
processes produced by brain damage. This leads to a regression of
dysfunction associated with the temporary "shock" to the neurons
in the vicinity of the lesion. Medical interventions that
facilitate these early recovery processes determine the extent to
which recovery will proceed to the subsequent stages.
... ... b) In the days and weeks following a stroke, the brain
begins active processes of recovery involving adaptive
plasticity. In the early stages, this may include intra-system
pathways, if any have survived undamaged, pathways that normally
play a mere supporting role in the undamaged brain. Since such
pathways have previously been involved in the task, only task
relearning is necessary, and this may explain why recovery is
sometimes seen within a few weeks following a stroke.
... ... c) But if there is complete damage to a neural system,
the brain may still have the capacity to recruit an alternative
brain system, one not generally activated for the task by normal
subjects. In such instances, the alternative system is naive to
the task, so that the patient must relearn the task more or less
completely. This requires more time, and evidence concerning
alternative system pathways was until recently unavailable.
     4) The authors conclude: "The existence of distinct stages
in the recovery process has only become evident through the use
of *functional imaging techniques. As the technology develops, we
have little doubt that we will come to appreciate progressively
finer aspects of adaptive plasticity and its role in a patient's
recovery from brain lesions such as stroke."
-----------
AS 2000 88:426
-----------
Notes:
... ... *inflammatory processes: In general, an "inflammatory
change" is a response of tissues to irritation or injury. The
response involves a dynamic complex of cellular and chemical
reactions that occur in the affected blood vessels and adjacent
tissues.
... ... *functional imaging techniques: The two main functional
brain imaging techniques are *functional magnetic resonance
imaging (fMRI) and *positron-emission tomography (PET).
... ... *functional magnetic resonance imaging (fMRI): We must
first distinguish between magnetic resonance imaging (MRI) and
"functional" magnetic resonance imaging (fMRI) as applied to the
brain. The former is essentially a technique for examining
morphology, while the latter is a technique for examining
activity of brain tissue. Both techniques involve computerized
analysis of data. In general, MRI involves magnetic coils
producing a static magnetic field parallel to the long axis of
the patient or subject, combined with inner concentric magnetic
coils producing a static magnetic field perpendicular to the long
axis. A radio-frequency coil specifically designed for the head
perturbs the static fields to generate a magnetic resonance
image. The interaction physics in this technique is that between
the magnetic fields and atomic nuclei in brain tissue. "Sliced"
views can be obtained from any angle, and the resolution is quite
high and on the order of millimeters for current magnetic field
strengths of 1.5 tesla. Functional magnetic resonance imaging
(fMRI), the variant of MRI discussed here, is based on the fact
that oxyhemoglobin, the oxygen-carrying form of hemoglobin, has a
different magnetic resonance signal than deoxyhemoglobin, the
oxygen-depleted form of hemoglobin. Activated brain areas utilize
more oxygen, which transiently decreases the levels of
oxyhemoglobin and increases the levels of deoxyhemoglobin, and
within seconds the brain microvasculature responds to the local
change by increasing the flow of oxygen-rich blood into the
active area. This local response thus leads to an increase in the
oxyhemoglobin-deoxyhemoglobin ratio, which forms the basis for
the fMRI signal in this technique. Because of its high spatial
resolution (millimeters) and high temporal resolution (seconds)
compared to other imaging techniques, fMRI is now the technology
of choice for studies of the functional architecture of the human
brain.
... ... *positron-emission tomography (PET): This is a technique
for producing cross-sectional images of the body after ingestion
and systemic distribution of safely metabolized positron-emitting
agents. The images are essentially functional or metabolic, since
the ingested agents are metabolized in various tissues.
Fluorodeoxyglucose and H(sub2)O(sup15) are common agents used for
cerebral applications, and in cerebral applications of central
importance to the technique is the fact that changes in the
cellular activity of the brains of normal, awake humans and
unanesthetized laboratory animals are invariably accompanied by
changes in local blood flow and also changes in oxygen
consumption.
-----------
SW 2000 22 Sep
-----------
SCIENCE-WEEK 12 Oct 2001 http://scienceweek.com
-------------------
Related Background:
EVIDENCE OF CROSS-MODAL PLASTICITY IN BLIND HUMANS
In neurobiology, the term "plasticity" is the name given to the
capacity of neural tissue to adjust to change. One variant of
this concerns the dependence of the "wiring" of the nervous
system on its input. Another variant concerns the degree to which
one region can under certain conditions assume the function of
another region. Plasticity does not occur everywhere in the
nervous system, but it is often evident in the cerebral cortex of
the brain, the cortex being the thin layer of cells apparently
responsible for higher analysis of sensory input, language,
ideation, and other so-called higher functions lumped together in
the category "cognitive processes". Last week Leonardo G. Cohen
et al (11 authors at 4 installations in US, AR, JP) reported the
results of studies of cross-modal plasticity in blind humans.
These studies involved non-invasive interference with cortical
activity by applying transient magnetic stimulation from outside
the skull. It has been demonstrated that such stimulation can
affect brain activity, and in this study the apparatus threshold
for stimulation of the motor cortex was first determined, and
then transient magnetic stimulation 10% above that threshold
applied to the occipital lobes of the brain through the overlying
skull to interfere with electrical activity in the visual cortex.
The experiments involved various location and procedural
controls, and also a group of sighted individuals. Essentially,
what was found is that in people blind from an early age, the
visual cortex is apparently involved in somato-sensory function
(fingertip reading of individual Braille characters), while the
same is not true for sighted subjects.
-----------
NAT 11 Sep 97
SW 26 Sep 97
-----------
SCIENCE-WEEK 12 Oct 2001 http://scienceweek.com
-------------------
Related Background:
BRAIN PLASTICITY IN CHILDREN AFTER HEMISPHERECTOMY
Epilepsy is a term unhappily applied to several dozen different
seizure disorders, their commonality being central nervous system
seizures rather than identical pathological processes causing the
seizures. From a neurophysiological standpoint, a seizure is the
end result of a massive discharge of nerve cells, often the motor
neuron pathways that activate muscle cells. Seizures can be
produced by various central nervous system infections, metabolic
disturbances, toxic agents, cerebral oxygen deficiency, expanding
brain lesions, cerebral trauma, cerebral hemorrhage, and so on.
In general, any physiological event or series of events that
produces a wide disruption of central nervous system activity has
the potential for production of seizures of one sort or another.
Most patients who for reasons known (symptomatic epilepsies) or
unknown (idiopathic epilepsies) are chronically subjected to
seizures can be helped with various pharmacological agents such
as phenytoin or cloneazepam, but 10% to 20% of patients have
seizures that cannot be managed by drugs. If the seizures are due
to a specific damaged locus in the brain (the "epileptic focus"),
the recourse for these patients, if the locus can be determined,
is surgery. What is done is to completely remove the epileptic
focus, sometimes an area no larger than a small coin, and if the
surgery is successful the cure is immediate and permanent. There
are cases, however, in which the affected part of the brain is
quite large, the seizures completely unmanageable, and the only
recourse is radical surgery. Since severe chronic epilepsy due to
brain lesions is usually first diagnosed in young children, it is
such children who are the usual patients in radical brain surgery
for epilepsy. The most radical and fairly common procedure is
hemispherectomy, removal of an entire half of the brain, and the
most remarkable aspect of this is that when the surgical
procedure is successful, not only are the seizures eliminated,
but the child can function as well or almost as well as any other
child. It is an example of a phenomenon well-known to
neurobiologists called "brain plasticity", the ability of the
brain to recover the function of a damaged or removed region by
assignment of the function to an undamaged location. The language
area of the brain, for example, is often considered to be fixed
on the left side of the brain by genetics, but in truth it is not
so fixed, and if the left side of the brain is removed at an
early age, the right side of the brain will quickly develop a
language center and there will be little functional impairment.
In a recent publication, Eileen P.G. Vining (Johns Hopkins
University, Baltimore MD US) reports the progress of 54 children
who underwent hemispherectomy for recurrent severe epileptic
seizures. The majority of the patients were seizure-free
following surgery, no longer needed drugs, and many of the
patients are now in school. One of the most significant facts
about the human brain is that its histological development
continues at least until adolescence, and the dynamism of this
histological development is what is responsible for its
remarkable plasticity.
-----------
Pediatrics August 1997
SW 22 Aug 97
-----------
SCIENCE-WEEK 12 Oct 2001 http://scienceweek.com

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

8. COMPUTER MODELS OF INVERTEBRATE SEGMENTATION
Eors Szathmary (Eotvos University, HU) discusses body
segmentation in invertebrates. It has long been known that the
beginning and the end of embryological development are variable
traits in evolution. Diversity at an early developmental stage
(in the mechanism of gastrulation, for example) can be attributed
to evolutionary adaptations to the ecological setting in which
the embryo begins to unfold. The later phases must also differ,
otherwise species would all look the same. For example,
development in parasitic wasps has diverged widely. Early cell
divisions of the fertilized egg, establishment of head-to-tail
polarity, and the genetic circuit for body segmentation have all
been modified, apparently as adaptations to the parasitic life-
style. But developmental malleability can go beyond this.
Although the external appearance of an organism may be fixed, the
genetic network, in which genes switch one another on and off so
that programmed development runs successfully, seems to be
changeable. This is analogous to rewiring a computer without
changing the housing. Segmentation, including stripes on animal
coats, fascinated the mathematician Alan Turing (1912-1954), who
in 1952 proposed a mechanism for pattern formation. Turing
demonstrated that in a chemical system that begins as spatially
homogeneous, a diffusing activator and an inhibitor could give
rise to stationary wave-like concentration profiles of chemicals.
Similar reaction-diffusion mechanisms may be at work in some
biological systems, but other systems, previously thought to be
Turing systems, such as stripe formation in the fruit fly
Drosophila, apparently use a mechanism in which stripe identity
is determined by differing combinations of regulatory elements,
following an initial spatial heterogeneity, with the underlying
genetic circuit having a hierarchical structure.
-----------
NAT 2001 411:143
-----------
SCIENCE-WEEK 12 Oct 2001 http://scienceweek.com

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

9. MISMATCH-REPAIR GENES AND GENOMIC STABILITY
R. Kucherlapati and R.A. DePinho (Albert Einstein College of
Medicine, US) discuss mismatch-repair genes. A human cell
contains nearly 6 billion base pairs of DNA, and with these huge
numbers, it is almost inevitable that during the lifetime of the
cell the DNA will accumulate errors from either environmental
influences or from mistakes in DNA replication. To repair such
damage to their genomes, all organisms have caretaker proteins,
including those of the DNA "mismatch-repair system". As well as
mending damaged DNA, mismatch-repair proteins also prevent
slightly dissimilar DNA strands from exchanging sequence
fragments (i.e., they prevent recombination). Therefore, it is
not surprising that genomes become unstable when their mismatch-
repair genes are mutated and no longer function. Because
mismatch-repair proteins have such a crucial role in mending
damaged DNA, errors accumulate more rapidly when the genes
encoding these proteins are mutated, with such mutations
predisposing humans to several different cancers. For example,
defects in one subset of mismatch-repair genes result in the
inherited cancer syndrome called hereditary non-polyposis
colorectal cancer. A good model to explain how the loss of
mismatch-repair genes leads to an increased susceptibility to
cancer is that as errors accumulate some will inactivate tumor-
suppressing genes or activate cancer-promoting genes (oncogenes),
until a critical threshold of tumor-promoting errors is reached.
-----------
NAT 2001 411:647
-----------
SCIENCE-WEEK 12 Oct 2001 http://scienceweek.com

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

10. ALZHEIMER'S DISEASE AND SECRETASES
W.P. Esler and M.S. Wolfe (Harvard University, US) discuss
Alzheimer's disease. First described by Alois Alzheimer (1864-
1915) in 1906, the disease that bears his name for the most part
remained an enigma until the last years of the 20th century.
Along with descriptions of progressive loss of memory and general
cognitive decline, Alzheimer noted the presence of intraneuronal
tangles and extracellular "amyloid" plaques in the disease-
damaged brain, but he could not decipher whether the tangles or
plaques were causative or merely markers of the disease. In 1991,
the search for genetic linkages yielded a major clue: Mis-sense
mutations in a specific protein (amyloid-beta precursor protein)
caused autosomal dominant early-onset (familial) Alzheimer's
disease, and these mutations occurred in and around the amyloid
beta-peptide region of the precursor protein. These findings,
together with observations that amyloid beta-peptides readily
form neurotoxic threadlike structures called "fibrils", bolstered
the view that the accumulation and deposition of amyloid beta-
peptides in the brain over decades leads to neuronal dysfunction
and eventually to clinical manifestation of the disease (the
"amyloid hypothesis"). The amyloid-beta precursor protein (APP)
is an integral membrane protein processed by several different
proteases called "secretases". The search for these secretases
has unexpectedly revealed secretase proteins that are also
involved in a signaling pathway essential for proper cell
differentiation during embryonic development, and one of these
proteins now appears to be a member of an emerging class of
polytopic membrane proteases that includes an unusual metallo-
protease involved in cholesterol biosynthesis.
-----------
SCI 2001 293:1449
-----------
SCIENCE-WEEK 12 Oct 2001 http://scienceweek.com

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

11. GLUTAMATE AND NEUROLOGICAL DISEASE
E.A. Cavalheiro and J.W. Olney (University of Sao Paulo, BR)
discuss glutamate and neurological disease. Forty years ago, it
was demonstrated by T. Hayashi that the amino acid glutamate,
when introduced directly into the central nervous system, could
trigger convulsions by an excitatory (depolarizing) action on
nerve cell membranes. At approximately the same time, other
researchers reported that subcutaneous injections of glutamate
can kill neurons in the retina or brain, and that the
neuroexcitatory action of glutamate was responsible for the cell-
killing effect. From these early findings, glutamate gradually
became recognized for its beneficial role as the predominant
excitatory neurotransmitter in the mammalian central nervous
system, and also became recognized for its detrimental potential
as an "excitotoxic" molecule that can destroy neurons throughout
the entire central nervous system. A large family of glutamate
transmitter receptors was then identified, with these receptors
classified as either "ionotropic" or "metabotropic". The
ionotropic subfamily is further divided into 3 subtypes, referred
to as N-methyl-D-aspartate (NMDA) receptors, alpha-amino-3-
hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) receptors, and
kainate receptors. In recent decades, it has been demonstrated
that glutamate excitotoxicity is responsible for neuronal
degeneration in anoxia and in essentially all other acute brain
injury conditions (e.g., stroke, hypoglycemia, epilepsy, and head
trauma), and the excitotoxic action of glutamate has been shown
in many cases to involve abnormal uptake or intracellular
mobilization of calcium ions. There is also substantial evidence
implicating abnormal glutamate signaling and/or excitotoxicity in
the pathogenesis of numerous more chronic central nervous system
diseases, such as Parkinson's and Alzheimer's disease, and also
multiple sclerosis.
-----------
PNAS 2001 98:5947
-----------
SCIENCE-WEEK 12 Oct 2001 http://scienceweek.com
-------------------
Related Background:
SECRETION OF GLUTAMATE BY BRAIN ASTROCYTES
Glial cells are more numerous than neurons in the brain, but
their function has been generally characterized as "metabolic" or
"supportive", without much discussion of details, and more is
known about peripheral glial cells than glial cells in the
central nervous system. Astrocytes are the largest glial cells,
with many extensions radiating outward like a starburst, and at
least one of their functions is apparently to maintain the so-
called "blood-brain barrier" effectively separating neural tissue
from blood. L-glutamate (derived from the amino acid, glutamic
acid) is considered the principal excitatory neurotransmitter in
the vertebrate central nervous system, and is one of the neuro-
transmitter substances that interact with ligand-gated ion
channels. Kainic acid, an algal neurotoxin, is a structural
analogue of glutamate, and it has been extensively used in
research, since at high concentrations it selectively destroys
glutamate receptor neurons (glutaminergic neurons). Glutamate is
known to act on 3 classes of receptors, one of them called the
kainate receptor because at low concentrations of kainic acid the
action of glutamate on this receptor is enhanced. The chemistry
of this kainate receptor is not yet well-characterized, mainly
because selective ligands for it are not known. Another class of
glutamate receptor is the AMPA receptor [AMPA = (RS)-alpha-amino-
3-hydroxy-5-methyl-4-isoxazoleproprionic acid], and the third is
NMDA (N-methyl-D-aspartate). These 3 receptors are ionotropic,
i.e., their activation produces changes in membrane ion
permeability. According to another and more recent scheme of
glutamate receptor classification, one receptor type is
AMPA/kainate (ionotropic), another receptor type is NMDA
(ionotropic), and a third receptor type is a slow-acting receptor
type coupled to G-proteins and called metabotropic receptors.
(The G-proteins are membrane-bound proteins that act as
transducers between messenger molecules interacting with the cell
surface and the intracellular messenger system). Prostaglandins
are fatty acids secreted by cells that have hormone-like actions
in the immediate vicinity, and one circumstance that produces
their release is tissue injury.
... ... Bezzi et al (8 authors at 2 installations, IT) report
that coactivation of the AMPA/kainate and metabotropic glutamate
receptors on astrocytes stimulates these cells to release
glutamate through a calcium-dependent process mediated by
prostaglandins. The authors suggest their results reveal a new
pathway of regulated transmitter release from astrocytes, and
that interactions between neurons and astrocytes may play a
critical role in synaptic plasticity and neurotoxicity. They also
suggest that the prostaglandin-mediated glutamate release from
astrocytes may be involved in the pathophysiology of various
brain diseases and injuries.
-----------
NAT 1998 15 Jan
SW 1998 30 Jan
-----------
SCIENCE-WEEK 12 Oct 2001 http://scienceweek.com

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

12. DEVELOPMENTAL POTENTIAL OF CLONED MAMMALIAN EMBRYOS
James C. Cross (University of Calgary, CA) discusses the
developmental potential of cloned mammalian embryos. Few recent
scientific advances have captured the imagination of biologists
and the general public like the prospect of animal cloning. The
procedure is elegantly simple: a nucleus from a mature cell is
transferred into the cytoplasm of an enucleated egg and the
nucleus becomes "reprogrammed" to reexecute embryogenesis. That
cloning has been successful at all seems biologically remarkable
and has forced biologists to assess what cell differentiation is
all about. However, although possible, the process has many
complications. Fetal and placental weight are often dramatically
increased. Animals also frequently suffer from congenital
anomalies and die within hours of birth. Embryonic and fetal
losses are also extremely high, such that far less than 1 percent
of manipulated embryos give rise to live-born animals. These grim
facts, collectively termed the "cloned offspring syndrome", have
raised considerable concern about the cloning process. The
reasons for these complications have remained a mystery, but
recent work has revealed surprising conclusions, and results
indicate that different aspects of cloned offspring syndrome are
attributable to distinct methodological problems. In particular,
poor embryonic and postnatal survival is not specifically
associated with cloning, and the underlying mechanistic defects
can now better be addressed by focusing on the effects of cell
culture conditions, embryo transfer, and so on.
-----------
PNAS 2001 98:5949
-----------
SCIENCE-WEEK 12 Oct 2001 http://scienceweek.com
-------------------
Related Background:
CLONED CALVES PRODUCED FROM ADULT CELLS AFTER LONG-TERM CULTURE
Broadly defined, cloning of a complete organism is asexual
reproduction that results in progeny genetically identical to the
parent. To many people, cloning was invented with the birth of
the sheep Dolly. In fact, cloning has been practiced for
millennia with plants, and for decades with mammals, and Dolly's
birth followed an orderly progression of experiments that started
with cloning mammalian embryos in the 1970s. The first successful
mammalian cloning by nuclear transfer, in which cells from
*cleavage-stage sheep embryos were fused with unfertilized sheep
eggs, was reported in 1986. Successful cloning from older embryos
(and ultimately from an adult cell, in the case of Dolly)
challenged conclusions from previous work that the nuclei of
differentiated cells are unable to support normal development.
Lives clones have been obtained from adult somatic cells in
sheep, mice, and cows, and *transgenic animals have been produced
by cloning *gene-transfected fetal somatic donor cells. But until
now, successful somatic cell cloning has been for the most part
limited to the use of donor cells either fresh or after only a
few *passages (under 10) in culture, which poses a problem for
targeted gene manipulations, since such manipulations usually
require long-term culture passages.
... ... C. Kubota et al (7 authors at 2 installations, JP US) now
report the birth of 6 clones of an aged (17-year-old) Japanese
Black Beef bull using ear-skin *fibroblast cells as nuclear donor
cells after up to 3 months of in vitro culture (10 to 15
passages). The authors report they observed higher developmental
rates for embryos derived from later passages (10 to 15) as
compared with those embryos from an early passage (passage #5).
Four surviving clones are now 10 to 12 months of age and appear
normal, similar to their naturally reproduced peers. The authors
suggest these data indicate that fibroblasts of aged animals
remain competent for cloning, and that prolonged culture does not
affect the cloning competence of adult somatic cells. The authors
conclude: "In this study, we demonstrated that adult somatic
cells remained *totipotent for cloning after long-term culture.
This suggests the feasibility of targeted genetic manipulations
such as *gene knockout using cultured somatic cells before
cloning to produce knockouts or other types of genetically
engineered cloned animals. Cloning using site-specific
genetically manipulated cells would be a valuable tool with
applications in agriculture, medicine, and basic biological
research."
-----------
PNAS 2000 97:990
-----------
Notes:
... ... *cleavage-stage: The early and rapid division stage that
divides the fertilized egg into smaller and smaller cells
(blastomeres) while retaining the same overall size of the
embryo.
... ... *transgenic animals: A "transgenic animal" is an animal
into which genetic material from another organism has been
transferred, the transferred and incorporated new genes then
being expressed with the resultant production of specific
proteins.
... ... *gene-transfected: "Transfection" is the uptake
of foreign (exogenous) DNA fragments in solution directly into
animals cells in laboratory culture, and is one method of
introducing foreign genes into cells.
... ... *passages: In this context, the term "passage" refers to
a replication of cells in culture, with each passage referring to
a single replication.
... ... *fibroblast cells: (fibroblasts) Fibroblasts are a type
of connective tissue cell, secreting structural proteins such as
collagen, the proteins forming a matrix in which the fibroblasts
become embedded. These cells can be easily obtained from skin,
and they can be easily cultured outside the body.
... ... *totipotent: "Totipotent" cells have the ability to
differentiate into any type of cell and thus form a new organism
or regenerate any part of an organism.
... ... *gene knockout: In this context, the term "knockout"
refers to an organism in which function of a specific gene has
been deleted by genetic engineering techniques.
-------------------
SW 2000 26 May
-----------
SCIENCE-WEEK 12 Oct 2001 http://scienceweek.com
-------------------
Related Background:
BIOTECHNOLOGY: ON THE FUTURE OF CLONING
During the past several years, research on cloning has produced
much discussion in the scientific community and a whirlwind of
media attention by journalists in books and magazine articles. It
is now possible to make clones, or exact genetic copies, of
sheep, cows, goats, mice and, probably, humans. Although there
are a number of social issues concerning the possibility of human
cloning that remain unresolved, what seems certain is that in the
future the technology of cloning will improve and the
applications of mammalian cloning will be of considerable
importance.
... ... J.B. Gurdon and A. Coleman (2 installations, UK) review
the current state of the science and technology of cloning, the
authors making the following points:
     1) The authors point out that cloning techniques have been
in use for centuries. The practice of taking cuttings is
universal among gardeners, and large companies now propagate
desirable plant strains in large quantities. Lower invertebrates
can be easily cloned: for example, if one cuts an earthworm or
flatworm in half, the halves will regenerate to create two
genetically identical individuals. Although this method does not
work in vertebrates, identical twins are naturally occurring
genetic clones, and the method of nuclear transplantation, first
used 40 years ago in frogs, has been successfully used to make
clones of various mammals, and could probably be applied to
humans.
     2) Of importance in nuclear transfer techniques is the
general scheme of natural fertilization: In vertebrates,
fertilization begins with the union of the sperm cell and the egg
cell. Prior to fertilization, the egg cell has been stopped at a
certain stage of the *cell-division cycle. The sperm provides an
activation stimulus that triggers the resumption and completion
of cell division. The egg and sperm "*pronuclei" then swell,
their chromosomes unravel from the tightly packed condensed state
in which they are stored, and DNA replication can proceed. The
chromosomes then recondense, the nuclear membrane dissolves, and
the fertilized egg cell divides into two identical daughter
cells.
     2) The technique of nuclear transfer subverts fertilization
by replacing the female genetic material of an unfertilized egg
cell with the nucleus from a different cell. The general
procedure of nuclear transfer in mammals is as follows:
... ... a) The genetic material is removed from the recipient
cell (an unfertilized egg cell).
... ... b) The genetic material of this egg cell is replaced by a
nucleus from a donor cell, the donor nucleus containing donor DNA
(the donor genome).
... ... c) The egg cell, now containing the donor nucleus, begins
the series of divisions that normally follow fertilization.
... ... d) At a very early embryonic stage (*blastocyst), the
embryo is transferred to a surrogate mother.
... ... e) In the surrogate mother, the embryo (fetus) develops
to term, is delivered as a neonate, and the neonate is
genetically identical to the donor of the original donor nucleus.
     3) The authors suggest that for successful cloning, it is
probably essential for donor nuclei to contain a full complement
of genes. For nuclear transfer to work, an adult cell that has
already been programmed (differentiated) into a specific cell
type needs to be somehow reprogrammed so that it regains the
genetic totipotency of sperm cells and egg cells (germline cells)
-- the ability to guide the formation of all the different cell
types that make up an animal. An important conclusion to come
from nuclear transfer experiments is that the processes of cell
differentiation and ageing do not lead to permanent genetic
changes in non-germline cells (somatic cells).
     4) The pattern of gene expression in adult cells is very
different from that in embryonic cells. In amphibians, for
example, a number of genes expressed in embryos 5 hours after
fertilization are not expressed in differentiated adult cells.
Conversely, some genes are expressed in adult cells but not in
early embryos. When embryos are analyzed a few hours after the
transfer of adult cell nuclei, gene expression cannot be
distinguished from that in embryos grown from normal fertilized
eggs. This indicates that the exchange of cytoplasm around a
nucleus, from the cytoplasm of an adult cell to that of an egg
cell, causes a dramatic switch in gene expression in only a few
hours. A nucleus that was once part of an intestine, skin, or
muscle cell is therefore transformed into that of an embryonic
cell. Key molecules found in egg cells that may bring about
reprogramming of the genome include *nucleoplasmin and certain
embryo-specific proteins around which the DNA is wrapped (embryo-
specific *histones).
     5) The authors suggest that one of the major uses for
cloning in the future may be "therapeutic cloning"  -- the use of
cloning to generate tissue to replace tissue that has been
damaged or diseased. The essential idea here is to use as a donor
nucleus in nuclear transfer the nucleus of a somatic cell of the
individual requiring therapeutic tissue replacement. The major
advantage of the technique is that transplantation of the cloned
tissue into the original donor should occur without the tissue
rejection that now compromises the success of transplantation
procedures: the cloned tissue would be genetically identical to
the patient's tissue. The authors suggest that therapeutic
cloning is "ethically less contentious because a new person is
not produced." However, since an unfertilized human egg cell must
be used in the procedure, "as for abortion, the issue of the
deliberate destruction of a potential person is raised."
-----------
NAT 1999 402:743
-----------
Notes:
... ... *cell-division cycle: The term "cell division cycle"
(cell cycle) refers to the ordered sequence of phases through
which a cell passes from one mitotic cell division to the next.
... ... *pronuclei: The term "pronucleus" refers to the nucleus
of either the egg cell (ovum) or the sperm cell following
fertilization. Once the ovum is fertilized, there are two
pronuclei, one originating from the ovum, the other from the
sperm cell that produced fertilization. The two nuclei do not
fuse until immediately before the first cleavage, when each
pronucleus loses its membrane to release its contents.
... ... *blastocyst: A mammalian egg in the later stages of
*cleavage but before implantation in the uterus. The blastocyst
consists of a hollow fluid-filled ball of cells and an inner cell
mass (embryonic stem cells) from which the embryo develops.
... ... *cleavage: See main report.
... ... *nucleoplasmin: A heat-stable acidic protein present in
the nucleus of many cell types. It forms complexes with
*histones.
... ... *histones: In *eukaryotic chromosomes, about every 200
nucleotides, the DNA double helix is coiled around a complex of 8
histone proteins, the entire assembly having the appearance of
beads on a string. The beads (nucleosomes) are in turn
supercoiled into a solenoid structure, and the entire complex of
the eukaryotic chromosome is called "chromatin". The small
histone proteins are basic (as opposed to acidic) proteins, and
they are essential in forming nucleosomes. Chemically, histones
are single polypeptide chains, molecular mass 11 to 21
kilodaltons, 25 percent lysine and arginine amino acids.
... ... *eukaryotic: Eukaryotic cells are cells having internal
membrane-bound organelles such as a nucleus.
-----------
SW 2000 4 Feb
-----------
SCIENCE-WEEK 12 Oct 2001 http://scienceweek.com
-------------------
Related Background:
ON THE MEDICAL APPLICATIONS OF CLONING
Ian Wilmut, who led the research team that cloned the sheep
Dolly, presents an essay describing the general techniques of
cloning and the possible medical applications. The author makes
the following points: 1) The author says the announcement of the
sheep Dolly's birth in February 1997 attracted enormous press
interest, perhaps because Dolly drew attention to the theoretical
possibility of cloning humans. The author says this is an outcome
he hopes never comes to pass. But the ability to make clones from
cultured cells derived from easily obtained tissue should bring
numerous practical benefits in animal husbandry and medical
science, as well as answer critical biological questions. (*Note
#1) 2) The ability to produce offspring from cultured cells opens
up relatively easy ways to make genetically modified (transgenic)
animals. Such animals are important for research and can produce
medically valuable human proteins. 3) Cloning offers many other
possibilities. One is the generation of genetically modified
animal organs that are suitable for transplantation into humans.
4) Another promising area is the rapid production of large
animals carrying genetic defects that mimic human diseases such
as *cystic fibrosis. 5) The power to make animals with precisely
engineered genetic constitution could also be employed more
directly in cell-based therapies for important diseases,
including *Parkinson's disease, *diabetes, and *muscular
dystrophy. 6) Cloning could also be a means of producing herds of
cattle that lack the *prion protein gene, which makes cattle
susceptible to infection with prions, the agents that cause "*mad
cow disease". 7) The cloning technique might curtail the
transmission of genetic disease by treating an embryo with
advanced forms of gene therapy to modify the nuclei of embryonic
cells so that the subsequent fetus and child was free of a
specific genetic disease and unable to pass the disease to the
next generation. 8) The author states that none of the suggested
uses of cloning for making copies of existing people is ethically
acceptable to his way of thinking, "because they are not in the
interests of the resulting child. It should go without saying
that I strongly oppose allowing cloned human embryos to develop
so that they can be tissue donors." The author concludes: "It
nonetheless seams clear that cloning from cultured cells will
offer important medical opportunities. Predictions about new
technologies are often wrong; societal attitudes change;
unexpected developments occur. Time will tell. But biomedical
researchers probing the potential of cloning now have a full
agenda."
-----------
SA December 1998
-----------
Notes:
... ... *Note #1: The cloning procedure here is based on nuclear
transfer and involves the use of two cells. The recipient cell is
usually an unfertilized egg cell taken from an animal soon after
ovulation. The DNA-containing chromosomes are removed from the
recipient cell, and then the donor cell (containing the genome to
be copied) is fused with the recipient egg cell, and the new
fused cell is stimulated to begin the normal process of embryonic
development. Essentially, the key event is the apparent
reprogramming of the adult somatic donor cell genome by the egg
cell cytoplasm so that the donor genome now behaves like the
genome of a fertilized embryonic cell and normal development
results.
... ... *cystic fibrosis: An inherited disease of the exocrine
glands, primarily affecting the gastrointestinal tract and
respiratory systems. The "exocrine" glands are glands that secret
material via excretory ducts (e.g., mucous secreting glands).
... ... *Parkinson's disease: A neurological disorder first
described by James Parkinson (1817) and associated with
degeneration of a specific small region of the brain and a
resultant loss of projection to several important brain centers.
... ... *diabetes: When used without a qualifier, this refers to
diabetes mellitus, a metabolic disease in which carbohydrate
utilization is reduced and that of lipid and protein enhanced,
the disease caused by an absolute or relative deficiency of the
hormone insulin.
... ... *muscular dystrophy: This is a general term for a number
of hereditary, progressive degenerative disorders affecting
skeletal muscles, and often other organ systems as well.
... ... *prion protein: Prions are a class of poorly understood
proteins implicated in a number of exotic human neurological
diseases and in some common animal diseases such as sheep scrapie
and bovine spongiform encephalopathy in cattle ("mad cow
disease").
... ... *mad cow disease: (bovine spongiform encephalopathy)
Although the precise structure of the infectious agent that
causes prion diseases is still unknown, important features of its
molecular genetics have been revealed, and the evidence suggests
possible transmissibility of bovine spongiform encephalopathy to
humans.
-----------
SW 1998 11 Dec
-----------
SCIENCE-WEEK 12 Oct 2001 http://scienceweek.com
-------------------
Related Background:
EIGHT CALVES CLONED FROM SOMATIC CELLS OF A SINGLE ADULT
The technique of nuclear transfer (nuclear transplantation),
which involves the transfer of a nucleus from one cell to another
cell whose nucleus has been previously removed, is an efficient
technique for assessing the developmental potential of a nucleus
and for analyzing the interactions between the donor nucleus and
the recipient cytoplasm. In amphibians, successful nuclear
transfer has been reported for the transfer of *blastula cells to
oocytes (egg cells), with successful development of cells into
tadpoles and juvenile frogs. Other cell types, including *germ
cells and somatic cells from tadpoles, have also been shown to
have developmental totipotency: their nuclei directed the
formation of fertile amphibians. However, despite extensive
studies in amphibians, progeny have not been generated from adult
cell nuclei. This obstacle was recently overcome in sheep and
mice, and nuclei from fetal *fibroblast cells have directed the
formation of lambs and calves. In 1998, nuclear transfer was
reported to have been successfully used to produce fertile mice
from *cumulus cells collected from *metaphase II oocytes.
... ... Y. Kato et al (8 authors at 3 installations, JP) now
report cloning of calves at a high rate using cumulus cells and
*oviductal epithelial cells that were *passaged several times in
vitro. The authors report that 8 calves were derived from
*differentiated cells of a single adult cow, 5 calves from
cumulus cells and 3 calves from oviductal cells, out of 10
embryos transferred to surrogate cows. All calves were visibly
normal, but 4 calves died at or soon after birth from
*environmental causes, and postmortem analysis revealed no
abnormality. The authors suggest these results demonstrate that
bovine cumulus and oviductal epithelial cells of the adult have
the genetic content to direct the development of newborn calves.
-----------
SCI 1998 282:2095
-----------
Notes:
... ... *blastula cells: The blastula is an early embryonic stage
in which the embryo is a hollow fluid-filled ball of cells one
layer thick.
... ... *germ cells and somatic cells: Germ cells are the
reproductive cells, egg cells and sperm cells, while somatic
cells are all other cells.
... ... *fibroblast cells: A type of connective tissue cell,
secreting structural proteins (e.g., collagen) that form certain
tissue components, including the extracellular matrix.
... ... *cumulus cells: Cells surrounding the ovulated mammalian
egg cell, and which quickly disperse in the presence of sperm.
... ... *metaphase II: In general, meiosis is the process of
reductive cell division leading to progeny cells containing half
the genetic complement of the parent cell. In animals, meiosis
occurs twice (a first meiosis and a second meiosis), and
metaphase II is one of the early stages of the second meiosis.
... ... *oviductal epithelial cells: In animals, epithelial cells
(epithelium) compose the cell layers that form the interface
between a tissue and the external environment, for example, the
cells of the skin, the lining of the intestinal tract, and the
lung airway passages.
... ... *passaged: In this context, the term "passage" refers to
a replication of cells in culture. The phrase "passaged several
times" refers to serial replication.
... ... *differentiated cells: Refers to developmental cell
specialization (morphology and biochemistry) resulting from
activation (and/or deactivation) of specific parts of the cell
genome.
... ... *environmental causes: In this study, one calf died from
pneumonia following heat stroke, and 3 calves died from
congenital birth dysfunctions or traumas. The other 4 calves
remained healthy.
-----------
SW 1999 19 Feb
-----------
SCIENCE-WEEK 12 Oct 2001 http://scienceweek.com
-------------------
Related Background:
CLONED TRANSGENIC CALVES FROM FETAL FIBROBLASTS
Research has been in progress for more than a decade to develop a
system for genetic modification and large-scale cloning in
cattle, an important species in agriculture, biotechnology, and
human medicine. During the past 18 months, there has been much
publicity concerning the cloning of sheep using somatic cell
donor cells, the research conducted by the Wilmut group in the
UK. ... ... Now Cibelli et al (8 authors at 3 installations, US)
report similar results (but with a different method) in cattle.
Actively dividing fetal fibroblasts were genetically modified
with a marker gene, a clonal line was selected, and the cells
were fused to enucleated mature oocytes. Out of 28 embryos
transferred to 11 recipient cows, three healthy, identical,
transgenic calves were generated. Furthermore, the life span of
near senescent donor fibroblasts could be significantly extended
by nuclear transfer. With the ability to extend the life-span of
these primary cultured cells, this system would be useful for
inducing complex genetic modification in cattle. The authors
suggest their somatic cell nuclear transfer procedure could
improve the efficiency of producing transgenic cattle and broaden
the scope of applications for transgenic cattle.
-----------
SCI 1998 280:1256
SW 12 Jun 98
-----------
SCIENCE-WEEK 12 Oct 2001 http://scienceweek.com

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

13. IN FOCUS: ON THE COPERNICAN REVOLUTION 
"The replacement of the planet Earth by the Sun as the center of
heavenly motions is widely (and rightly) seen as one of the great
scientific paradigm shifts of all time. But what is often
misunderstood is the reason why this Copernican "revolution"
eventually carried the day with the scientific community. The
commonly held view is that Copernicus's heliocentric model
vanquished the competition, especially the geocentric view of
Ptolemy, because it yielded better predictions of the positions
of the celestial bodies. In actual fact, the predictions of the
Copernican model were a little _worse_ than those obtained via
the complicated series of epicycles and other curves that
constituted the Ptolemaic scheme, at least to within the accuracy
available using the measuring instruments of the time. No, the
real selling point of the Copernican model was that it was much
_simpler_ than the competition yet still gave a reasonably good
account of the observational evidence. The Copernican revolution
is a good case study in how to wield Ockham's Razor to slit the
throat of the competition. When in doubt, take the simplest
theory that accounts for the facts. The problem is that it's not
always easy to agree on what is 'simple'. The notion of
simplicity, like truth, beauty, and effective process, is an
intuitive one, calling for a more objective characterization --
that is, formalization -- before we can ever hope to agree about
the relative complexities of different theories."
-----------
J.L. Casti and W. DePauli: _Goedel: A Life of Logic_
(Perseue Publishing, Cambridge MA 2000, p.166)
http://www.amazon.com/exec/obidos/ASIN/0738205184/scienceweek
-----------
SCIENCE-WEEK 12 Oct 2001 http://scienceweek.com

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

14. SW ARCHIVE: 
ON THE SOKAL HOAX AND PHILOSOPHICAL EXTRAPOLATIONS IN PHYSICS
In the last quarter of this century, many fields outside of
physical science are apparently in the throes of epistemological
crises that are seen as originating in similar crises in physics
during the first quarter of the century. *Complementarity,
uncertainty, relativity, observer interactions -- the perceived
philosophical implications of these ideas have been imported into
the humanities and social sciences where they have rocked
foundations and produced what many critics view as an
intellectual babble. In 1996, theoretical physicist Alan Sokal
concocted an article consisting mostly of the ideations of so-
called "*postmodern" cultural studies of science, the article
concerned with "a transformative hermeneutics of quantum gravity"
and purporting to be an application of theoretical physics to
affirm the thrust of postmodern cultural studies of science in
the humanities and social sciences. The article was accepted and
*published by the journal *Social Text*, and shortly afterward,
in the journal *Lingua Franca*, Sokal revealed that his article
was a complete hoax and designed as a parody of contemporary
postmodern thought. In the academic furor that followed, Sokal's
article was characterized as "an ingenious exposure of the
decline of intellectual standards in contemporary academia," and
"a brilliant parody of the postmodern nonsense rampant among the
cultural studies of science." ... ... Writing in a physics
journal, M. Beller now outlines an argument that theoretical
physicists both past and present have had much responsibility for
what appear to be the nonsensical applications of theoretical
physics to the humanities and social sciences. The author makes
the following points: 1) The philosophical pronouncements
(several of which are quoted at length by Beller) of theoretical
physicists *Niels Bohr, *Max Born, *Werner Heisenberg, *Wolfgang
Pauli, and *Pascual Jordan deserve some of the blame for the
excesses of the postmodern critique of science. 2) Like the
deconstructionist *Jacques Derrida, Bohr was notorious for the
obscurity of his writing. Yet physicists relate to the
obscurities of Derrida and Bohr in fundamentally different ways:
Derrida is treated with contempt and Bohr is treated with awe,
his obscurity attributed to "depth and subtlety". 3) The author
points out that in a widely used compendium of papers in
theoretical physics published in 1983, there is an often cited
reprinted paper by Bohr whose pages are out of order, and yet no
complaints are heard and the mistake, which occurs in both
hardcover and softcover editions, is apparently rarely noticed.
3) The author points out that Bohr intended his philosophy of
complementarity to be an overarching epistemological principle
applicable to physics, biology, psychology, and anthropology.
Pauli argued for application of the quantum concept of reality to
unify science, religion, Jungian archetypes, and extrasensory
perception. Born stated that quantum philosophy would help
humanity cope with the postwar era. Heisenberg expressed the hope
that the results of quantum physics would transform cultural life
by producing a renaissance of ideas. Jordan explored the "formal"
parallels between quantum physics and Freudian psychoanalysis. 4)
Beller points out that the philosophical pronouncements of Bohr
and other founders of quantum physics are not just an
anachronistic curiosity, since contemporary popular writings by
physicists and science writers continue to proclaim the victory
of Bohr's conception of reality, even though the Copenhagen
"orthodox" interpretation of quantum physics -- the abandonment
of causality and the ordinary conception of reality -- is not the
only possible interpretation of quantum physics, and ultimately
it might not even be the surviving one. 5) Beller concludes: "The
opponents of the postmodernist cultural studies of science
conclude confidently from the Sokal affair that 'the emperors
have no clothes.' But who, exactly, are all these naked emperors?
At whom should we be laughing?"
-----------
M. Beller (Hebrew University Jerusalem, IL): The Sokal hoax: at
whom are we laughing?
(Physics Today September 1998)
QY: Mara Beller, Hebrew University, Jerusalem IL.
-----------
Text Notes:
... ... *Complementarity: The idea that a fundamental particle is
neither a wave nor a particle, because these are complementary
modes of description (see below, Report #6).
... ... *postmodern: The term here refers to studies of how
contemporary concepts and methods are determined by historical or
ideological context. So, for example, one set of postmodern
questions concerning science involves the influences of Western
socio-political ideology on the structure and methods of Western
science. The general idea is the consideration of science as a
product of the culture from which it arises. But the term
"postmodern" has a loose usage, with one meaning in literature,
another in art, and a third in the social sciences.
... ... *published: Sokal's paper was published in *Social Text*
(Spring/Summer 1996, p.216), and then exposed immediately by
himself in *Lingua Franca* (May/June 1996, p.62).
... ... *Niels Bohr (1885-1962): Nobel Prize in Physics 1922. He
worked in the fields of atomic structure and nuclear fission, and
he proposed the doctrine of complementarity. As director of the
Institute of Theoretical Physics in Copenhagen from 1920 on, Bohr
was the head of what came to be called the Copenhagen School of
Quantum Mechanics, which produced what came to be called the
"Copenhagen orthodoxy" view of the implications of quantum
mechanics as applied in general to theoretical physics.
... ... *Max Born (1882-1970): Nobel Prize in Physics 1954. Did
fundamental work in quantum theory, particularly work linking the
wave function of the electron to electron distribution
probability. It was Born who apparently coined the term "quantum
mechanics". Born worked with Werner Heisenberg, one of his
students, in the development of the mathematical techniques of
matrix mechanics, an alternative to the Schroedinger wave 
equation for calculation of the position and momentum of the
electron in the atom. From Born: "I am now convinced that
theoretical physics is actual philosophy."
... ... *Werner Heisenberg (1901-1976): Nobel Prize in Physics
1932. Developed quantum theory and formulated the uncertainty
principle, which concerns matter, radiation, and their reaction,
and which places absolute limits on the achievable accuracy of
measurement of physical phenomena in the quantum domain.
... ... *Wolfgang Pauli (1900-1958): Nobel Prize in Physics 1945.
Originated the exclusion principle, which states that in a given
system no two fermions (electrons, protons, neutrons, or other
elementary particles of half-integral spin) can be characterized
by the same set of quantum numbers. He also predicted the
existence of neutrinos.
... ... *Pascual Jordan (1902-1980): Worked with Born and
Heisenberg in the development of matrix mechanics. Also worked
in the relativistic quantum field theory of electromagnetism
(quantum electrodynamics). 
... ... *Jacques Derrida (1930- ): A philosopher whose work spans
literary criticism, psychoanalysis, linguistics, and philosophy,
with an emphasis on the primacy of written text, the
referentiality of language, and the objectivity of conceptual
structures. Founded the school of criticism known as
"deconstruction". 
-------------------
SW 1998 25 Sep
-----------
SCIENCE-WEEK 12 Oct 2001 http://scienceweek.com

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

15. SOURCES:
AS: Amer. Scientist; CEN: Chem. & Eng. News; GD: Genes & Dev.;
GR: Genome Res.; JACS: J. Amer. Chem. Soc.; JAMA: J. Amer. Med.
Assoc.; JCE: J. Chem. Educ.; MMWR: CDC Morbidity and Mortality
Weekly Report; NAT: Nature; NATM: Nature Medicine; NEJM: New
Engl. J. Med.; NS: New Scientist; NYT: New York Times; NYR: New
York Review; PNAS: Proc. Natl. Acad. Sci.; PRL: Phys. Rev. Lett.;
PT: Physics Today; SA: Scientific American; SCI: Science; SW:
ScienceWeek; TS: The Scientist.

In the text, the affiliation following the author's name is the
affiliation of the lead author.

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

NOTICES
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

CHANGE OF EMAIL ADDRESS:
If at any time you need to change the Email address at which you
receive SW, please send the information to:
request@scienceweek.com

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-= 

SCIENCE-WEEK SUBSCRIPTIONS:
Complete subscription information is available at:
http://scienceweek.com/subinfo.htm

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

We welcome comments, suggestions, and criticisms from our
subscribers. Public letters relevant to any report are also
welcome. Editorial contact: editors@scienceweek.com

Editor/Publisher: Dan Agin
Managing Editor: Claire Haller
Associate Editor: Joan Oliner

Copyright (c) 1997-2001 SCIENCE-WEEK/Spectrum Press Inc.
All Rights Reserved
US Library of Congress ISSN 1529-1472

---------------------------------------------
ScienceWeek is published by Spectrum Press Inc.,
3023 N. Clark Street #109, Chicago, 60657-5205 IL, USA.
---------------------------------------------
-----end file