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.

April 9, 1999 -- Vol. 3 Number 15

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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

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Contents of This Issue:

1. On Physics, Biology, and Cartoons
2. On Reactions on Semiconductor Surfaces
3. Evidence for an Early Opening of the Bering Strait
4. Isotopic Analysis of the Diet of an Early Hominid
5. On the Neurobiological Mechanisms of Memory
6. Measuring Oncogenic Effects of Single Alpha Particles

-- In Focus: On Methods in Theoretical Physics

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

1. ON PHYSICS, BIOLOGY, AND CARTOONS
Each generation of scientists, it seems, passes through a phase
of bemusement with the idea that the application of physics to
biology will yield sudden and enormous rewards. Such a phase
occurred at the turn of the century, then again in the 1930s, and
again in the 1950s, and apparently still again in our present
era. In a lead editorial, the journal _Nature_ presents the
following headline: Can Physics Deliver Another Biological
Revolution? In the unsigned editorial, the author makes the
following points: 1) The main method of analysis in molecular
biology has been the cartoon representation of networks,
pathways, and complexes. "Indeed, superb papers have been written
for the purpose of adding a single arrow to an existing cartoon.
But to really understand the biochemical network thus represented
one needs to have numbers attached to the arrows, and equations
relating the numbers." 2) The author suggests there is nothing
new in biologists opting tools from the physical sciences, or of
physicists "doing physics" in biological systems. What is
apparently new, the author suggests, is that many physicists are
currently excited by the challenge of tackling important
questions in biology, using both the physical and mental tools of
physics, and that US funding agencies are apparently eager to
support such endeavors. 3) But the author suggests one should not
underestimate the extent of this challenge: Physicists are
addicted to simplification -- a habit viewed with suspicion by
biologists. And the theoretical physicist will find that most
molecular biologists have little time for mathematical theory,
which has played no significant role in their field's great
advances. 4) Nevertheless, there is apparently a considerable
will to overcome existing conceptual and institutional
obstacles... "Today, with physicists who can manipulate single
molecules in the laboratory, and simulate and quantitatively
analyze complex systems, who can say what might not be possible?"
[*Note #1]
-----------
[unsigned]: Can physics deliver another biological revolution?
(Nature 14 Jan 99 397:89)
QY: Philip Campbell [nature@nature.com]
... ... *Note #1: Irrespective of any ephemeral bemusements (some
of which may derive from current funding allocations), the impact
of physics on biology is continuing and pervasive: Physics
provides the foundations of new technology, and new technology
provides for new experimental approaches in biology. A similar
paradigm exists for the impact of chemistry on biology. These
paradigms have existed for the past three centuries, and they are
apparently of the utmost significance for any "revolutions" in
biology. Indeed, the revolutions in biology, in this century at
least, have most often depended on new tools rather than on new
concepts borrowed from the physical sciences. In the 1930s, for
example, many biologists and some physicists were enamored of the
idea of applying the principles of thermodynamics to biological
systems. The results of such applications were far from seismic.
It was the soon to be introduced electron microscope that
essentially finished the transition from classical biology to
modern biology. Following that transition, the dramatic and rapid
flowering of molecular biology had more to do with new techniques
involving the ultracentrifuge and electrophoresis than with new
concepts derived from the physical sciences. Nevertheless, since
a so-called "living" system is indeed a complex physical system
existing under specific physical constraints, any direct
application of the concepts of physics to biology has potential
significance and should be encouraged.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 9Apr99
-------------------
Related Background:
BIOLOGY FUNDING VS. PHYSICS FUNDING: UNEASE EXPRESSED
The journal _Nature_, in a recent editorial, criticizes US
President Bill Clinton for asserting that the next 50 years will
be "very likely characterized predominantly as the age of
biology." The journal also criticizes the emphasis on the news of
biology, "trumpeted by the media worldwide". Politicians ought to
understand, *Nature* says, that the results of physics "have a
way of unobtrusively and unpredictably invigorating apparently
unrelated disciplines and technologies, even to a revolutionary
extent..." Ergo, support for the physical sciences continues to
be in the best interests of society.
(Nature 8 Jan 98) (Science-Week 23 Jan 98)
-------------------
Related Background:
ON FASHIONS IN SCIENCE AND TECHNOLOGY
Rolf Landauer (IBM Corp., US), in a review of fashions in science
and technology, points out both the negative and positive aspects
of such fashions in general, and in particular in his own field,
condensed matter physics. Among other problems, Landauer notes:
1) Fashions in science and technology draw attention away from
other deserving areas. 2) Funding agencies make an apparently
sensible initial decision to support a particular exploratory
scientific path, but they too easily become emotionally tied to
their choice. 3) The competition for grants and employment causes
public relations activities to have an increasing greater role in
the practice of science. 4) Whereas in the past judgments in an
institution about the quality of a colleague's work were based on
an assumed understanding of that work, at present promotions
depend on the ability to get funding, citation index scores,
etc., and in-house evaluations often are less important than
external evaluations. 5) These days a single publication is lost
in the deluge of papers, and the only way to be heard in the
scientific community is to repeatedly publish essentially the
same information over and over again. This produces a large
publication volume per researcher, which in turn forces other
researchers to do the same if they want to advance in status in
their installations and in their field. As any working scientist
is aware, these are only some of the problems inherent in the
present structure of professional science. Landauer suggests that
fashions in science have a mostly negative impact, and that more
serious debate is needed about how fashions affect professional
science and the training of new scientists.
QY: Rolf Landauer, Thomas J. Watson Research Center, IBM Corp.,
Yorktown Hts, NY US.
(Physics Today December 1997) (Science-Week 12 Dec 97)


2. ON REACTIONS ON SEMICONDUCTOR SURFACES
Chemical reactions on surfaces are important in many areas of
science and technology. On metal surfaces, the electronic states
of the surface atoms are spatially extended and can therefore be
easily shared with those of reactive species, the result a
dramatic influence on the structure of these species as they
approach the surface. In contrast, bonding on semiconductor
surfaces is largely covalent, and surface electronic states tend
to be spatially localized. ... ... Harry E. Ruda (University of
Toronto, CA) presents a short review of current research
concerning reactions on semiconductor surfaces, the author making
the following points: 1) Understanding of the interactions of
species with semiconductor surfaces has been considerably
advanced by the widespread use of *scanning tunneling microscopy
(STM), which can probe, with atomic resolution, the spatial
extent of electron density on a surface. 2) Bias-dependent
scanning tunneling microscopy studies, in which images are taken
at different voltages between the STM tip and the sample, allow
the determination of the energy spectra of surface electronic
states, and in special cases enable discrimination between
different chemical species. 3) Coupled with computer modeling,
which can provide increasingly realistic descriptions of the
pertinent underlying physics, scanning tunneling microscopy
studies are providing  the information needed to understand and
control the interactions of chemical species on semiconductor
surfaces. The author concludes: "This research will have a
profound influence on nanotechnology, slated to become the
cornerstone of coming generations of semiconductor devices and
circuitry."
-----------
Harry E. Ruda: Reactions on semiconductor surfaces.
(Science 29 Jan 99 283:646)
QY: Harry E. Ruda [ruda@edf.utoronto.ca]
-----------
Text Notes:
... ... *scanning tunneling microscopy: First available in the
early 1980s, this technique involves an atomically sharp metal
tip brought in atomic proximity (e.g., 0.5 to 1 nanometer) to a
flat surface so that electrons can *tunnel between the two
systems. Recording the atomic modulation of the atomic structure
which scanning the tip across the surface allows one to image
adsorbed species and surface morphologies.
... ... tunnel: Tunneling is a quantum mechanical phenomenon
involving an effective penetration of an energy barrier resulting
from the width of the barrier being less than the wavelength of
the particle.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 9Apr99
-------------------
Related Background:
ELECTRICAL MEASUREMENTS ON SINGLE METAL ATOMS
Fabrication of structures at the atomic scale is now possible
using techniques for manipulation of individual atoms, and there
is thus a prospect of designing electrical circuits atom by atom.
A prerequisite for successful design of such circuits is
knowledge of the relationship between the macroscopic electrical
characteristics of a circuit and the quantum properties of the
individual atoms used as building blocks. ... ... Scheer et al (9
authors at 4 installations, FR ES NL) report that chemical
valence determines the conduction properties of the simplest
imaginable circuit -- a one-atom contact between two metallic
banks. The authors report that the extended quantum states that
carry the current from one bank to the other proceed through the
valence orbitals of the constriction atom. They considered the
idea that the number of current-carrying modes or channels of a
one-atom contact is determined by the number of valence orbitals,
and so should strongly differ for metallic elements in different
series of the periodic table. The authors tested this conjecture
using *scanning tunneling microscopy and mechanically
controllable *break-junction techniques to obtain atomic size
constrictions for four different metallic elements (Pb, Al, Nb,
Au), covering a broad range of valences and orbital structures.
The authors suggest their results demonstrate unambiguously a
direct link between valence orbitals and the number of conduction
channels in one-atom contacts, and that this cannot be understood
within a free-electron model. They suggest that only a
microscopic model that takes into account the atomic orbital
structure as well as the local atomic geometry can fully explain
the conduction properties of these contacts. The authors further
suggest that these concepts will be applicable in slightly
modified form to conduction through clusters of atoms and
molecules.
QY: Elke Scheer [Elke.Scheer@phys.uni-karlsruhe.de]
(Nature 9 Jul 98 394:154) (Science-Week 7 Aug 98)
-------------------
Related Background:
... ... *scanning tunneling microscopy: This is essentially an
instrument for producing surface images with atomic-scale lateral
resolution using a fine-probe tip raster-scanned over the surface
at a distance of 0.5 to 1 nanometer, with the resulting
*tunneling current (or position of the tip required to maintain a
constant tunneling current) monitored. The technique can be used
to manipulate single atoms or small groups of atoms, given
atomically smooth substrates in ultra-high vacuum and at low
temperature.
... ... *break-junction: A "break" junction is an extremely
narrow separation of two conductors, narrow enough so that an
electron tunneling gap is established. One way to achieve such a
separation is to literally break a conductor to achieve the
required gap.
... ... *tunneling current: In general, a tunnel junction is a
junction (potential barrier) involving a thin separation between
two conductors, with the width of the junction equal to or less
than the wavelength of the conductance entity (e.g., the
wavelength of the electron). The significant result at a tunnel
junction is that the conductance entity can penetrate the barrier
by means of quantum mechanical "tunneling", this tunneling effect
essentially arising from the fact that with the wavelength of the
particle larger than the width of the potential barrier, the
barrier is effectively transparent to the particle.
-------------------
Related Background:
A SINGLE-CARBON NANOTUBE ROOM-TEMPERATURE TRANSISTOR
Carbon nanotubes are similar to fullerenes, except their shape is
tubular. They were first discovered by Sumio Iijima (NEC
Laboratories, JP) in 1991, they come in both multi-walled and
single-walled versions, and they have diameters of the order of
10 to 30 nanometers. The use of individual molecules as
functional electronic devices was first proposed by Aviram and
Ratner in 1974. Since then, molecular electronics has attracted
much interest, particularly because it could lead to conceptually
new miniaturization strategies in the electronics and computer
industry. But the realization of single-molecule devices has
remained a challenge, largely owing to difficulties in achieving
electrical contact to individual molecules. Recent advances in
nanotechnology, however, have resulted in electrical measurements
on single nano-scale molecules. ... ... Tans et al (3 authors at
Delft University of Technology, NL) report the fabrication of a
field-effect transistor -- a 3-terminal switching device -- that
consists of one semiconducting single-wall carbon nanotube
connected to 2 metal electrodes. By applying a voltage to a gate
electrode, the nanotube can be switched from a conducting to an
insulating state. The device operates at room temperature,
thereby meeting an important requirement for potential practical
applications. Electrical measurements on the nanotube transistor
indicate that its operation characteristics can be qualitatively
described by the semi-classical band-bending models currently
used for traditional semiconductor devices, an unexpected result.
The authors suggest the fabrication of this 3-terminal switching
device at the level of a single molecule represents an important
step towards molecular electronics.
QY: Cees Dekker (dekker@qt.tn.tudelft.nl)
(Nature 7 May 98 393:49) (Science-Week 29 May 98)
-------------------
Related Background:
EXPERIMENTAL STUDY OF CONDUCTANCE AT A MOLECULAR JUNCTION
... In recent years, a number of laboratories have used [break]
junctions to examine the electrical properties of various organic
substances sequestered in the junction gap. The idea is to test
the validity of charge transport approximations at the molecular
level. Charge trans- port, or charge transfer, in the general
sense, is simply the movement of electric charge (electrons) from
one place to another, which means it includes effective movement
from one part of a single molecule to another part of the same
molecule. Since the movement of electric charge is electric
current, if means can be found to control the process at the
molecular level, one has the beginnings of molecular-electronics.
... ... M. A. Reed et al (Yale University, US; University of
South Carolina, US) report the formation of a mechanically
controllable break junction involving gold electrodes coated with
benzene-1,4-dithiol. The statically stable gold-sulfur-aryl-
sulfur-gold junction allowed direct observation of charge
transfer through the molecules. The authors suggest this study
provides a quantitative measure of the conductance of a junction
containing a single molecule, making it a fundamental step in
molecular-scale electronics.
QY: M. A. Reed, Yale Univ., Elect. Engin. (203) 432-4771.
(Science 10 Oct 1997) (Science-Week 31 Oct 97)


3. EVIDENCE FOR AN EARLY OPENING OF THE BERING STRAIT
The first opening of the Bering Strait is a datum of importance
in paleogeography, biogeography, and global oceanography. A
closed strait joined Eurasia and North America into one
supercontinent and allowed the interchange of terrestrial animals
and plants, but sealed off the marine connection between the
North Pacific-North Atlantic on one side and the Arctic Ocean on
the other side. The opening of the strait produced a dramatic
change in the composition of Arctic, North Atlantic, and North
Pacific shallow-water marine animals, temporarily ended
terrestrial migration between Asia and North America, and allowed
marine organisms to migrate between the Arctic and North Pacific
oceans for the first time since the middle *Cretaceous period.
But despite the apparent importance of the first opening of this
waterway, the event has apparently never been precisely dated,
and it has thus not been accurately incorporated into models of
global biogeography and oceanography. ... ... L Marincovich Jr.
and A. Yu. Gladenkov (2 installations, US RU) now present an
analysis of both *mollusc and *diatom fossils in the region. The
authors report that data for various species of marine diatoms
found with the *bivalve mollusc Astarte suggests an age range of
4.8 to 5.5 million years ago, and that *stratigraphic information
indicates this may be a minimum age range for the first opening
of the strait. The authors propose a range of between 4.8 and
7.3-7.4 million years ago. The authors emphasize their results
contrast with past studies which have suggested an age of 3.1 to
4.1 million years ago for the initial opening of the Bering
Strait.
-----------
L. Marincovich Jr. and A. Yu. Gladenkov: Evidence for an early
opening of the Bering Strait.
(Nature 14 Jan 99 397:149)
QY: Louie Marincovich Jr. [lmarin@best.com]
-----------
Text Notes:
... ... *Cretaceous period: The Cretaceous period is the
geological period ranging approximately from 146 million years
ago to 65 million years ago.
... ... *mollusc: Member of a phylum of bilaterally symmetrical
unsegmented invertebrates (e.g., snails, clams, oysters, squid,
etc.)
... ... *diatom: Also called bacillariophytes. Microscopic
unicellular eukaryotic algae; differentiated into approximately
10,000 different species.
... ... *bivalve mollusc: In this context, the term "bivalve"
refers to the presence of a hinged shell.
... ... *stratigraphic information: The term "stratigraphy"
refers to the study of layered sedimentary or metamorphic rocks,
especially their relative ages and the correlations between
different areas. (In general, "sedimentary rock" is any rock
formed by the consolidation of sediment, and "metamorphic rock"
is any rock resulting from partial or complete recrystallization
under temperature and pressure conditions elevated with respect
to the Earth's surface.)
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 9Apr99


4. ISOTOPIC ANALYSIS OF THE DIET OF AN EARLY HOMINID
The term "hominid" refers to any primate in the human family
(Hominidae) of which Homo sapiens (modern man) is the only living
specimen. The current consensus, based on molecular evidence, is
that our closest living relatives, gorillas and chimpanzees,
probably separated from our line (or us from them) approximately
6 to 8 million years ago. Humans, gorillas, common chimpanzees
and pygmy chimpanzees, the 4 African species of "great apes",
apparently had common ancestors perhaps 10 to 12 million years
ago. The first record of human footprints, of hominids walking
upright, was discovered at *Laetoli in East Africa, and has been
dated at 3.6 million years ago. This ancestor, Australopithecus
afarensis, probably weighed 25 to 50 kilograms (60 to 120 lbs.)
as an adult (*Note #1). Apparently derived from Australopithecus
afarensis were several species, including Australopithecus
africanus, a species which is believed to have appeared
approximately 3 million years ago. Little is known about the
diets of hominids that predate the Homo genus, because these
hominids did not leave archeological traces such as "*kitchen
middens" and stone tools. Consequently, researchers have made
inferences concerning hominid diet on the basis of craniodental
morphology, gross dental wear, and dental microwear. The current
consensus is that the 3-million-year-old Australopithecus
africanus hominid subsisted on fruits and leaves, similar to the
modern chimpanzee. Early hominid diets are of some theoretical
significance, since one current view is that the emergence of the
more intelligent Homo genus depended on the consumption of high-
quality animal foods that made possible biological changes
resulting in the evolution of a larger brain.
... ... M. Sponheimer and  J.A. Lee-Thorp (2 installations, US
ZA) now report a stable carbon isotope analysis of A. africanus
fossils from *Makapansgat Limeworks, South Africa. The authors
sampled 4 of the 14 Australopithecus africanus individuals that
have been unearthed at that location, and also analyzed the
dental enamel of associated 3-million year old animals (65
individual animals from 19 mammalian taxa) in order to place A.
africanus within a broader ecological context. The authors report
their results demonstrate that A. africanus ate not only fruits
and leaves, but they also ate large quantities of carbon-13
enriched foods such as grasses and sedges, or they ate animals
that ate these plants, or both. The authors suggest their results
indicate that early hominids such as A. africanus regularly
exploited relatively open environments such as woodlands or
grasslands for food, and that early hominids may have consumed
high-quality animal foods before the development of stone tools
and the origin of the genus Homo.
-----------
M. Sponheimer and J.A. Lee-Thorp: Isotopic evidence for the diet
of an early hominid, Australopithecus africanus.
(Science 15 Jan 99 283:368)
QY: Matt Sponheimer, Rutgers Univ. New Brunswick 908-932-8789.
-----------
Text Notes:
... ... *Laetoli: The discovery involved a 30-yard-long footprint
trail of three bipedal individuals, the trail made approximately
3.6 million years ago in a newly deposited layer of volcanic ash.
The ash layer also contains the prints of many other animal
forms. 
... ... *Note #1: The famous skeleton of "Lucy", discovered in
the 1970s, is an example of an Australopithecus afarensis fossil.
... ... *kitchen middens: In general, a "midden" is a refuse
heap. In this context, a "kitchen midden" is a mound consisting
of shells of edible molluscs and other refuse, the mound marking
the site of a prehistoric human habitation.
... ... *Makapansgat: (Makapansgaat) A cave site northeast of
Johannesburg.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 9Apr99
-------------------
Related Background:
HUMAN NEUROCOGNITIVE ARCHITECTURE: A PLASTICITY MODEL
In human neurobiology, the term "cognition" refers to
intellectual functions that include perceiving, remembering,
imagining, conceiving, understanding, judging, and reasoning. And
one of the central problems of human neurobiology is to
understand the neurological substrates for all of these aspects,
and also to understand the evolution of these aspects where such
evolution can be delineated. In other words, from a neurological
standpoint, the questions in this context are how does the mind
work and how did it get that way? From any research perspective,
that is what is called a tall order. One view, proposed by
evolutionary psychologists, is based on the presumption that the
demands on *hunter-gatherer life during the *Pleistocene epoch
generated a vast array of evolutionary cognitive adaptations that
determine current human cognition and behavior. But many
neurobiologists disagree with this approach, and instead focus on
the intrinsic *plasticity of the human brain, and in particular
on the intrinsic plasticity of the human neocortex, an intrinsic
plasticity manifested during individual development -- a response
to the individual's physical and psychological environment. These
two approaches are in essence restatements of the classical
nature vs. nurture controversy, but the classical character of
the question does not make the question less important. ... ...
P. La Cerra and R. Bingham present a critique of the evolutionary
psychology approach to the understanding of cognitive processes
and offer an alternative model which they propose is more in
agreement with the current evidence in neurobiology. The authors
make the following points: 1) An extensive literature underscores
the enormous functional plasticity of the *neocortex, a
distinguishing characteristic of mammals. This evidence supports
the position that cortical representational features are
systematically constructed by the dynamic interaction between
environmentally derived neural activity and intrinsic neural
growth mechanisms. 2) The information-processing capacities of
the neocortex are largely constructed in response to the problem
domains confronting the individual throughout development, and
these constructions remain modifiable throughout the life
history. 3) This neurobiological account of the ongoing
construction of the human neurocognitive architecture contrasts
sharply with the account of evolutionary psychologists, who
conceive of the mind as a confederation of information-processing
adaptations, each of which evolved in response to a problem posed
by Pleistocene selection pressures. 4) Numerous methodological
problems and theoretical flaws call the validity of the
evolutionary psychological paradigm into question... Evolutionary
psychologists have suggested that investigation of the neural
correlates of behavior is not mandatory for the study of
cognitive adaptations. This failure to reconcile theoretical
claims with neurobiological data has veiled from evolutionary
analyses the functional organization of the information-
processing circuits that comprise the human neurocognitive
architecture. 5) The authors propose that the problems faced by
ancestral *hominids and their mammalian predecessors would have
required an adaptively flexible online information-processing
system, and would have driven the evolution of a functionally
plastic neural substrate, the neocortex, rather than a
confederation of evolutionary prespecified social cognitive
adaptations. 6) The authors propose that human cognitive
processes result from the activation of constructed cortical
representational networks, which reflect probabilistic
relationships between sensory inputs, behavioral responses, and
adaptive outcomes. The construction of these networks throughout
development, and their modification throughout experience, are
mediated by subcortical circuits that are responsive to the life
history regulatory system. The authors conclude: "The model we
have outlined emphasizes individual differences as the product of
an evolved self-adapting system, a neurocognitive architecture
that is unique by design." In summary, the La Cerra and Bingham
idea is essentially that human neurocognitive systems (the
neurocognitive "architecture") are "constructed" during
individual development and experience, rather than inherited as
preformed circuits (structures) selected by evolutionary
pressures during and before the Pleistocene epoch. The authors
term their approach "constructivist".
-----------
P. La Cerra and R. Bingham (Calif. Inst. of Tech., US)
The adaptive nature of the human neurocognitive architecture: An
alternative model.
(Proc. Natl. Acad. Sci. US 15 Sep 98 95:11290)
QY: Roger Bingham [bingham@bbb.caltech.edu]
-----------
Text Notes:
... ... *hunter-gatherer life: The consensus among
paleoanthropologists is that sometime between the beginning of
*hominid bipedalism (the "hominini") and the appearance of Homo
sapiens, perhaps about 2 to 3 million years ago, there occurred a
divergence from essential ape-like behavior and the emergence of
a hunter-gatherer existence, the hunting of animals and the
gathering of plants, both for food.
... ... *hominids: In general, any primate in the human family.
... ... *Pleistocene epoch: A geological epoch with the time-
frame 2.5 million years ago to 11,000 years ago. This was the
epoch of rapid hominid evolution, and the appearance of cattle
and the modern horse.
... ... *plasticity: In neurobiology, the term "plasticity" is
the name given to the capacity of neural tissue to adjust to
change. One variant of this concerns the dependence of the
"wiring" of the nervous system on its input. Another variant
concerns the degree to which one region can under certain
conditions assume the function of another region. Plasticity does
not occur everywhere in the nervous system, but it is often
evident in the cerebral cortex of the brain, the cortex being the
thin layer of cells apparently responsible for higher analysis of
sensory input, language, ideation, and other so-called higher
functions lumped together in the category "cognitive processes".
... ... *neocortex: The most recently evolved part of the
cerebral cortex.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 23Oct98


5. ON THE NEUROBIOLOGICAL MECHANISMS OF MEMORY
One of the central problems in neurobiology concerns the
identification of the mechanisms involved in what we call
"memory". Possible mechanisms can be discussed at several levels,
ranging from new neuronal connections involving global brain
circuits to molecular mechanisms at the level of single
*synapses. ... ... J.E. Lisman and J.R. Fallon (2 installations,
US) present a short review of single-synapse molecular memory
mechanisms, the authors identifying the following possibilities,
each of which has some experimental evidence to sustain it: 1)
*Second messenger switch. This mechanism involves a positive
feedback loop between two enzymes, *protein kinase C and
*mitogen-activated protein kinase, with a so-called "second
messenger" intervening in each arm of the loop. 2) Kinase switch.
This is a simplified version of the previous switch, in this case
a shorter positive feedback loop without the intervening second
messengers. 3) *Transcriptional switch. This positive feedback
loop involves so-called "*transcriptional factors", DNA, and
*gene expression, 4) *Translational switch. This positive
feedback loop involves *messenger RNA (mRNA) and a second
messenger, with a protein produced by messenger RNA as an
intermediate, the second messenger feeding back to the synthesis
of the protein. 5) Structural unit with turnover. This mechanism
involves dynamic structural changes at the cell membranes
involved in the synapse, the changes producing an improved
connection, with the improvement either transient or relatively
permanent. 6) Structural unit without turnover. This mechanism
involves essentially static structural changes at the synaptic
cell membranes, the changes relatively permanent. The
neurobiological basis of memory has been a seductive puzzle for
several generations of neurobiologists, but although
considerations have moved to the molecular level, there is
apparently as much speculation as existed 50 years ago. In this
report, the authors conclude: "None of the proposed models have
been firmly excluded, and there seems to be no clear leading
candidate."
-----------
Editor's note: In addition to the background material below, see
the SW Focus Report "Neurobiology: Human Brain Plasticity and
Memory" available at URL http://scienceweek.com/swfr.htm
-----------
J.E. Lisman and J.R. Fallon: What maintains memories?
(Science 15 Jan 99 283:339)
QY: Justin R. Fallon [justin_fallon@brown.edu]
-----------
Text Notes:
... ... *synapses: The junction between the terminal of a
neuron's axon and another neuron.
... ... *Second messenger: In general, the "first messenger" is a
chemical entity that interacts with a receptor on the surface of
a cell, and the "second messenger" is an internal messenger that
results from that interaction and which interacts in turn with
some internal control process.
... ... *protein kinase C: In general, a kinase is an enzyme that
catalyzes the transfer of a phosphate group from one compound to
another. A protein kinase is an enzyme that phosphorylates one or
more hydroxyl or phenolic groups in proteins, with adenosine
triphosphate (ATP) being the phosphoryl-group donor. A protein
kinase C is a protein kinase requiring anionic phospholipid for
activity.
... ... *mitogen-activated protein kinase: A "mitogen" is any
substance or agent that stimulates or induces mitosis (cell
division).
... ... *Transcriptional switch: In this context, transcription
is the process by which the genetic information in DNA is
converted into RNA. 
... ... *transcriptional factors: A class of DNA-binding proteins
that regulate RNA transcription.
... ... *gene expression: In general, the term "gene expression"
includes any gene activity, but particularly an activity that
produces the synthesis or activation of a specific protein. 
... ... *Translational switch: In this context, translation is
protein synthesis, the process during which polypeptides are
synthesized on ribosomes in accordance with RNA code.
... ... *messenger RNA (mRNA): The ribonucleic acid molecule
transcribed from DNA that carries the coded information
specifying the sequence of amino acids in a protein.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 9Apr99
-------------------
Related Background:
BRAIN ACTIVITY CORRELATES OF VISUAL AND VERBAL MEMORY
In contemporary human neurobiology, memory is categorized into
two types: declarative memory (available to consciousness) and
procedural memory (generally not available to consciousness).
Declarative memory includes memory for such things as daily
episodes, words and their meanings, and history. Procedural
memory includes motor skills, associations, puzzle solving
skills, and so on. Identification of the neurological correlates
of memory in humans has until recently been based on slow
advances produced primarily by clinical evidence resulting from
localized traumatic injuries and localized tissue damage caused
by various diseases (all termed "lesions"). But the pace of
research in this field has now markedly increased due to several
new imaging techniques that allow identification of brain regions
activated in normal conscious subjects during various mental
tasks. The technique called "*functional magnetic resonance
imaging" (fMRI) is now an ascendant methodology, and this is the
technique that forms the basis for this report. (fMRI technical
details are provided in the notes below.) From clinical data
involving brain damage, it has long been known that one region
essential for declarative memory is the *medial temporal lobe of
the brain: bilateral damage to this brain region produces global
amnesia, a pervasive memory deficit for all new events and new
facts. There is additional brain damage evidence that regions of
the frontal lobes also contribute to declarative memory. Memory
deficits resulting from unilateral medial temporal lobe or
frontal lobe damage are often specific, with left-side lesions
impairing verbal memory, and right-side lesions impairing
nonverbal memory. Brain lesion studies, however, cannot
distinguish whether a given brain region normally participates in
the encoding of ongoing experiences into memories, or the storage
of the memories over time, or the later retrieval of those
memories. In contrast, the newer methods of functional
neuroimaging can indeed make such distinctions. ... ... J.B.
Brewer et al report the use of event-related functional magnetic
resonance imaging to identify specific brain activations that
differentiated between visual experiences that were later
remembered well, remembered less well, or forgotten. During fMRI
scanning of medial temporal lobe and frontal lobe regions,
subjects viewed complex color photographs, and subjects later
received a test of memory for the photographs. The authors report
their results indicate that the degree of activation in right
frontal lobe and bilateral *parahippocampal regions measures how
well a particular visual experience is encoded, and that the
degree of activation therefore predicts whether the visual
experience will be remembered well, remembered less well, or
forgotten by the individual. ... ... In a contiguous paper, A.D.
Wagner et al report a study of human brain activation during word
encoding, the study involving two different experimental designs
and the use of functional magnetic resonance imaging to examine
how brain activation differs for subsequently remembered and
subsequently forgotten verbal experiences. The authors report
their results indicate the ability to later remember a verbal
experience is predicted by the magnitude of activation in left
*prefrontal and temporal cortices during the experience. The
authors suggest these findings provide direct evidence that left
prefrontal and temporal regions jointly promote memory formation
for verbal experiences.
-----------
J.B. Brewer et al (5 authors at Stanford University, US): Making
memories: Brain activity that predicts how well visual experience
will be remembered.
(Science 21 Aug 98 281:1185)
QY: James B. Brewer [brewer@psych.stanford.edu]
A.D. Wagner et al (8 authors at Harvard University, US): Building
memories: Remembering and forgetting of verbal experiences as
predicted by brain activity.
(Science 21 Aug 98 281:1188)
QY: Anthony D. Wagner [adwagner@nmr.mgh.harvard.edu]
-----------
Text Notes:
... ... *functional magnetic resonance imaging: First, we
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.
... ... *medial temporal lobe: The temporal lobes are roughly the
lower sides of the brain, above the ears and behind the temporal
bones of the skull, but when the human brain is viewed from the
side, as it usually is in common gross depictions, the large and
functionally important ventral and infolded parts of the temporal
lobes are not visible. In general, the larger anatomical regions
of the human brain are best visualized as highly corrugated
lobular structures extensively folded and densely packed to fit
inside the volume-limiting protective skull. But isolated verbal
descriptions of the architecture are of limited use: anatomical
graphics are the best sources for visualization of gross brain
structures.
... ... *parahippocampal regions: These are parts of the temporal
lobes, visible only when the temporal lobes are unfolded away
from the main brain mass.
... ... *prefrontal: The portion of the frontal lobes anterior
to the motor region.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 2Oct98
-------------------
Related Background:
A NEW TYPE OF SYNAPTIC PLASTICITY OF NEOCORTICAL NEURONS
The term "synaptic plasticity" refers to a changeability of
synaptic connections and/or the efficacy of particular connect-
ions. "Cultured neurons" are embryological neurons separated from
the animal and growing and making connections in a suitable
experimental chamber. Glutamate is a major excitatory amino acid
neurotransmitter (transmitter substance at synapses) in the
brain, involved in about 40% of all brain activity. The term
"Hebbian modification" (named after the neuropsychologist Donald
Hebb) refers to the Hebbian "rule" that essentially states that
when one nerve cell repeatedly activates another nerve cell,
changes involving growth or metabolism occur in one or both nerve
cells that increase the efficiency of the activation.
... ... Turrigiano et al (5 authors at Brandeis University, US)
report a new form of synaptic plasticity in cultured neurons that
increases or decreases the strength of all of a neuron's synaptic
inputs as a function of activity, the changes partly due to
postsynaptic alterations in the response to glutamate. The
authors suggest that such "synaptic scaling" may help prevent
saturation of firing rates during developmental changes in the
number and strength of synaptic inputs, may stabilize synaptic
strengths during Hebbian modification, and may facilitate
competition between synapses and associated elimination of
synapses during development.
QY: Gina G. Turrigiano [turrigiano@binah.cc.brandeis.edu]
(Nature 26 Feb 98) (Science-Week 13 Mar 98)
-------------------
Related Background:
INTEGRIN-MEDIATED SHORT-TERM MEMORY IN DROSOPHILA
Complementing more than a century of research by psychologists on
human memory, recent animal behavioral and cellular studies have
also revealed two broad categories (or phases) of memory: short-
term memory and long-term memory. Short-term memory, lasting from
minutes to hours, is believed to involve rapid and transient
biochemical changes in nerve cells that affect the dynamics of
synapses, while long-term memory, which lasts from days to years,
is believed to involve restructuring of synapses as a result of
altered gene expression. In general, sensory conditioning
involves an effective neural coupling between a previously
neutral sensory stimulus (S1) and a particular organismic
response (R) when that stimulus is temporally coupled (preceding)
another stimulus (S2) that is not neutral and for which the
organism is hard-wired to produce the same response (R). The
classical paradigm is the Pavlovian dog salivating (R) in
response to a bell (S1) after the sound of the bell has been
associated with the presentation of food (S2). In the context of
this report concerning the fruit fly Drosophila, the term
"olfactory conditioning" refers to an avoidance conditioning
procedure involving the pairing of the presentation of an odor
with aversive electroshock, and the quantitative analysis of
behavioral results used to assess learning and memory perform-
ance. The term "plasticity" as used in this report refers to the
alteration of the behavior of nerve cells and of the organism as
a whole, in particular as an apparent result of experience.
Alpha-integrin is a type of cell surface receptor known to
mediate cell adhesion and chemical messenger signal transduction.
... ... Grotewiel et al (5 authors at Baylor College of Medicine,
US) report the isolation of a new Drosophila memory gene,
[volado] (called [vol]), which encodes a new alpha-integrin, and
that [vol] mutations have a dominant effect on short-term memory
following olfactory conditioning. Conditional expression of [vol]
just before training rescues the memory deficit of [vol] mutants.
The rescue is reversible, supporting a dynamic role for integrins
in neuronal and behavioral plasticity. The authors suggest that
integrin-mediated signaling or synaptic restructuring underlie
the formation, stability, or retrieval of short-term memory.
QY: Ronald L. Davis [rdavis@bcm.tmc.edu] (Nature 29 Jan 98)
-------------------
Related Background:
INTEGRIN CHANGES AND REGULATION OF NEURON ADHESION
The integrins are a family of glycoprotein cell membrane recept-
ors that bind to extracellular matrix components at the outer
membrane surface, and interact with cytoskeletal components at
the inner membrane surface. Integrins are thus important in cell-
extracellular matrix interactions and in cell-cell adhesion,
which makes them a central component in the formation and struct-
ure of various tissues. Cell adhesion is simply the ability of
cells to remain in association with each other. Sensory neurons
are nerve cells specifically designed to act as energy trans-
ducers, or to receive input from energy transducers, and to
produce an output that is propagated to other nerve cells. Nerve
cells in tissue culture (and nerve cells in a developing nervous
system and nerve cells undergoing regeneration) exhibit growth of
axons and dendrites, and this growth is called "neurite out-
growth". M. L. Condic and P. C. Letourneau (University of Utah,
US; University of Minnesota, US) report that the concentration of
integrin ligand regulates the amount of integrin receptor
expressed on the surface of sensory neurons, with the relation-
ship being inverse -- when ligand concentration is low, integrin
receptor amount increases -- and that ligand concentration
determines surface concentrations of integrin by changing the
rate at which the receptor is removed from the cell surface. In
addition, increased expression of integrin at the cell surface is
related to increased neuronal cell adhesion and neurite out-
growth. The authors suggest that integrin regulation is the key
process in the development and regeneration of nerve cell axons.
QY: M. Condic [maureenc@mailman.med.utah.edu] (Nature 23 Oct 97)
-------------------
Related Background:
A PROPOSAL FOR MEMORY SUPPRESSOR GENES
One of the central problems in neurobiology is to delineate the
mechanisms involved in information storage -- in the human
context, memory storage. How do neurons and neural circuits and
neural systems retain information about their past history, and
how does the past history influence present activity? When we
evoke a memory, a visual image of a rose, for example, where and
how is this image stored in the brain, and how is it evoked into
consciousness? Most neurobiologists believe that important
aspects of the memory/information storage process involve changes
in synaptic connections, the connections between neurons, and the
term "synaptic plasticity" refers to the changeability of neur-
onal synaptic connections, usually as a result of ongoing neural
activity. Tumor suppressor genes are sequences of DNA that code
for proteins that prevent or inhibit the growth of tumors.
... ... Now Abel et al (4 authors at Columbia Univ., US), in a
review of the relation between synaptic plasticity and memory
storage, propose that by analogy to tumor suppressor genes, the
restraint of synaptic growth involved in inhibitory restraints on
memory storage should be termed "memory suppressor genes". The
authors suggest that because these suppressor genes modulate or
gate other signaling pathways rather than directly activate them,
drugs targeted at memory suppressor gene products may prove to be
more therapeutically precise than those targeted at positive
regulators of memory storage.
QY: Eric R. Kandel, Columbia Univ. 212-854-1754
(Science 16 Jan 98) (Science-Week 30 Jan 98)


6. MEASURING ONCOGENIC EFFECTS OF SINGLE ALPHA PARTICLES
Domestic exposure to radon gas in homes is generally considered
to be the single largest naturally occurring environmental
hazard. The basic mechanism involves DNA damage to
*bronchioepithelial cells by alpha particles emitted by radon
decay progeny. Recent estimates (1998) are that 10 to 14 percent
of all lung cancer deaths in the US, or 15,400 to 21,800 deaths
per year, are linked to radon gas exposure from the environment.
At domestic exposure levels, the relevant bronchial cells are
very rarely traversed by more than one alpha particle, whereas at
higher radon levels these bronchial cells are frequently exposed
to multiple alpha-particle traversals. It is at the higher radon
exposure levels that epidemiological studies in uranium miners
have allowed lung-cancer risks to be quantified with reasonable
precision. Measuring the oncogenic transforming effects of
exactly one alpha particle without the confounding effects of
multiple traversals has hitherto been unfeasible, resulting in
uncertainty in extrapolations of risk from high radon levels to
domestic radon levels. ... ... R.C. Miller et al (Columbia
University, US) now report a technique to assess the effects of
single alpha particles on *cultured cells, the technique using a
charged-particle microbeam which irradiates individual cells or
cell nuclei with predefined exact numbers of particles. The
authors report that although the technique was previously too
slow in data acquisition to assess the relevant small oncogenic
risks, recent improvements in the technique now permit microbeam
irradiation of large numbers of cells, allowing the first
oncogenic risk measurements for the traversal of exactly one
alpha particle through a cell nucleus. The authors report that in
mouse *fibroblast cells the measured oncogenicity from exactly
one alpha particle was significantly lower than that expected
from statistical extrapolation, implying that cells traversed by
multiple alpha particles contribute most of the risk. The authors
suggest that if this result applies generally, extrapolation from
high-level radon risks (involving cellular traversal by multiple
alpha particles) may overestimate low-level radon risks
(involving only single alpha particles).
-----------
R.C. Miller et al: The oncogenic transforming potential of the
passage of single alpha particles through mammalian cell nuclei.
(Proc. Natl. Acad. Sci. US 5 Jan 99 96:19)
QY: David J. Brenner [djb3@columbia.edu]
-----------
Text Notes:
... ... *bronchioepithelial cells: In animals, epithelial cells
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.
The term "bronchioepithelial cells" refers to epithelial cells of
the lung bronchi (lung airway passages).
... ... *cultured cells: In general, the term "cultured cells"
refers to a population of cells maintained in vitro, the cells
proliferating in a medium of controlled composition. In many
experiments, the cultured cells are subpopulations of "immortal"
cell lines widely used in numerous laboratories.
... ... *fibroblast cells: A type of connective tissue cell,
secreting structural proteins (e.g., collagen) that form certain
tissue components.
-------------------
Related Background:
LOW LEVEL ASBESTOS EXPOSURE: DANGEROUS OR NOT DANGEROUS?
Asbestos is a commercially relevant group of strong, ductile, and
fire-resistant mineral fibers. These properties, which differ
among different mineralogic types of asbestos, strongly affect
its in vivo persistence and toxicity. Chrysotile asbestos
constitutes approximately 99 percent of airborne asbestos fibers
in the general environment. Heavy industrial exposure to asbestos
causes lung cancer and mesothelioma (a cancer of one of the
layers of cells lining various body cavities), but it is not
clear whether much lower environmental exposure to asbestos also
causes these cancers. Various regulatory agencies have estimated
the risk of cancer from low asbestos exposure by extrapolating
from the data for high asbestos exposure.
... ... Camus et al (3 authors at 3 installations, CA) tested the
prediction model used by the US Environmental Protection Agency
(EPA), by examining the predicted risk of asbestos-induced lung
cancer in a population of women with relatively high levels of
nonoccupational exposure to asbestos. Mortality among women in 2
chrysotile-asbestos mining areas of the province of Quebec (CA)
was compared with mortality among women in 60 control areas. The
EPA model, applied to the measured asbestos concentrations in the
local air, predicts approximately 75 excess deaths from lung
cancer in the mining-area population. The authors report their
study indicates between 0 and 6.5 excess deaths from lung cancer
in the population (relative risk = 1.0). The authors conclude
they found no measurable excess risk of death due to lung cancer
among women in two chrysotile-asbestos mining regions, and that
the EPA model overestimated the risk of asbestos-induced lung
cancer by at least a factor of 10. In an editorial rebuttal to
this paper, P.J. Landrigan (Mount Sinai School of Medicine New
York, US) makes the following points: 1) All forms of asbestos
are carcinogenic. All have been shown in clinical, epidemiologic,
and laboratory studies to be fully capable of causing lung
cancer, mesothelioma, and the full range of asbestos-related
diseases. All forms appear to be equipotent in the capacity to
cause cancer of the lung. 2) The most plausible explanation of
the low mortality from lung cancer observed in the Camus et al
study is that the women in the mining areas were exposed to an
asbestos aerosol in which many particles were too large to reach
their lungs. Previous studies have indeed established that the
risk of cancer in the mining and milling industry is much lower
than that in the industries that process and use asbestos, such
as textile manufacture and insulation. In mining and milling,
many large asbestos particles are suspended in the air, and they
tend not to reach the pulmonary alveoli as efficiently as small
particles. Thus, air sampling based on light microscopy in the
mining environment produces a spuriously high estimate of true
alveolar exposure. 3) Landrigan says: "Camus et al go beyond
their data when they assert, without qualification, that the
EPA's model overestimates the risk of lung cancer among persons
with nonoccupational exposure to asbestos by at least a factor of
10. The EPA's current regulatory controls embody a level of
caution commensurate with the hazard." 4) Chrysotile-asbestos is
still indisputably a human carcinogen, and this is also true for
Canadian chrysotile. Camus et al did, in fact, find the risk of
lung cancer associated with residence in the asbestos mining
areas to be more than 7 times that in non-mining areas
(standardized mortality ratio = 7.63). Landrigan concludes:
"Assertions that chrysotile can be used without risk in
developing nations are contrary to fact and extremely dangerous."
QY: Michel Camus, Institut Armand-Frappier, 531 Boul. des
Prairies, Laval, QC H7V 4Z3, CA.
QY: Philip J. Landrigan, Mount Sinai School of Medicine, New
York, NY 10029 US.
(New England J. Med. 28 May 98 338:1565,1618)
(Science-Week 26 Jun 98)


=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
 
IN FOCUS: ON METHODS IN THEORETICAL PHYSICS

"The methods of progress in theoretical physics have undergone a
vast change during the present century. The classical tradition
has been to consider the world to be an association of observable
objects (particles, fluids, fields, etc.) moving about according
to definite laws of force, so that one could form a mental
picture in space and time of the whole scheme. This led to a
physics whose aim was to make assumptions about the mechanism and
forces connecting these observable objects, to account for their
behavior in the simplest possible way. It has become increasingly
evident in recent times, however, that nature works on a
different plan. Her fundamental laws do not govern the world as
it appears in our mental picture in any very direct way, but
instead they control a substratum of which we cannot form a
mental picture without introducing irrelevancies. The formulation
of these laws requires the use of the mathematics of
transformations. The important things in the world appear as the
invariants (or more generally the nearly invariants, or
quantities with simple transformation properties) of these
transformations. The things we are immediately aware of are the
relations of these nearly invariants to a certain frame of
reference, usually one chosen so as to introduce special
simplifying features which are unimportant from the point of view
of general theory. The growth of the use of transformation
theory, as applied first to relativity and later to the quantum
theory, is the essence of the new method in theoretical physics."

-- P.A.M. Dirac: _The Principles of Quantum Mechanics_ 4th ed.
   (Oxford U. Press, London 1958, p.vii) [The quotation is from
   the Preface to the 1st edition, published 1930] 


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