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 2, 1998 -- Vol. 2 Number 40

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Geological time inspires awe, and there are no
certainties about the future, but perhaps it is
almost certain that someday they will collect our
skulls and call us Early Man.
-- Anonymous

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Contents of This Issue:

1. A Critique of Kuhn's Analysis of Scientific Revolutions
2. US Agency Calls for Biosciences PhD Freeze
3. Evidence Concerning Local Expansion Rate of the Universe
4. Geology: 1.4 Billion-Year-Old Unaltered Cosmic Spherules
5. Magnetic Levitation of Ordinary Objects
6. Chemical Alteration of Single Cells with Electroporation
7. Molecular Biology: Apoptosis, Mitochondria, and Caspases
8. Brain Activity Correlates of Visual and Verbal Memory

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1. A CRITIQUE OF KUHN'S ANALYSIS OF SCIENTIFIC REVOLUTIONS
Thomas Kuhn (1922-1996), a philosopher of science, published the
1st edition of ~The Structure of Scientific Revolutions~ in 1962.
The 2nd edition appeared in 1970, by which time the small book
was already established as a classic. Kuhn's focus was the
scientific "revolution", the abrupt shift in what he termed the
"paradigm" (theoretical framework) prevalent in a field at a
particular time. His idea was that if the change in a theoretical
framework is both intensive and extensive, the paradigm shift
results in a completely new way of looking at the data and
problems of the field, and if the discipline has universal
significance, the paradigm shift results in a new way of looking
at the world. Examples of the larger paradigm shift are the
Newtonian and Darwinian theories. Kuhn argued that scientific
development is cyclical, essentially moving from orthodoxy to
paradigm shift to orthodoxy. Later in his career, Kuhn became
identified with the idea that social and cultural conditions
affect the direction of science to an extent previously
unrecognized (essentially by promoting certain paradigm shifts
and hindering others), and this idea engendered an increase in
studies by social scientists of the cultural determinants of
methodologies and ideational frameworks in science. Kuhn's early
work was in general well-received by the scientific community,
but the later application of his ideas by the social sciences to
studies of the cultural determinants of science met with
considerable irritation among many physical and biological
scientists, who found unacceptable the notion of strong cultural
determinants assuming primacy of importance over the objectivity
of the scientific method and scientific attitude. ... ... In a
critical review of Kuhn's ideas concerning scientific
revolutions, physicist *Steven Weinberg now makes the following
points: 1) Kuhn reached radically skeptical conclusions
concerning what is accomplished in the work of science, and these
conclusions have made Kuhn a hero to the philosophers,
historians, sociologists, and cultural critics who question the
objective character of scientific knowledge, and who prefer to
describe scientific theories as social constructions not so
different from democracy or baseball. 2) Kuhn made the shift from
one paradigm to another seem more like a religious conversion
than an exercise of reason... Kuhn did not deny there is progress
in science, but he denied that it is progress ~toward~ anything.
3) It is not true, as Kuhn believed, that scientists are unable
to "switch back and forth between ways of seeing," and that after
a scientific revolution they become incapable of understanding
the science that went before it... Meanings can change, but
generally they do so in the direction of an increased richness
and precision of definition, so that we do not lose the ability
to understand the theories of past periods of normal (orthodox)
science. 4) Scientific revolutions do not necessarily change the
way we assess our theories: it is not true that different
paradigms lack a basis of comparison of one with the other. 5)
Even more radical than Kuhn's notion of the incommensurability of
different paradigms is his conclusion that in the revolutionary
shifts from one paradigm to another we do not move closer to the
truth... Kuhn does not distinguish between the durable and
ephemeral parts of physical theory, between the durable equations
that work and the ephemeral interpretations of why the equations
work. 6) Kuhn overestimated the degree to which scientists during
a period of normal (orthodox) science are captives of their
paradigms. Many scientists remain skeptical about the ephemeral
parts of their own theories. For example, the present theory of
the Standard Model for elementary particles has been tremendously
successful in accounting for the measured properties of the
particles, but physicists today are not firmly committed to the
view of nature on which it is based. 7) Revolutions in science
seem to fit Kuhn's description only to the extent that they mark
a shift in understanding some aspect of nature from pre-science
to modern science. The birth of Newtonian physics was a mega-
paradigm shift, but nothing that has happened in our
understanding of motion since then -- not the transition from
Newtonian to Einsteinian mechanics, or from classical to quantum
physics -- fits Kuhn's description of a paradigm shift.
-----------
Steven Weinberg (University of Texas Austin, US): The revolution
that didn't happen.
(New York Review of Books 8 Oct 1998 45:48)
QY: Steven Weinberg, University of Texas Austin 512-471-3434.
-----------

Text Notes:
... ... *Steven Weinberg (1933- ): Weinberg received the Nobel
Prize in Physics in 1979 for his theoretical work unifying the
weak nuclear force and the electromagnetic force. He shared the
prize with Abdus Salam, who independently achieved the same
result. Their work was based on the work of Sheldon Glashow, who
shared the prize with them that year.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 2Oct98


2. US AGENCY CALLS FOR BIOSCIENCES PHD FREEZE
In a report released September 10th, the US National Research
Council proposes that the number of PhD students in the life
sciences should be frozen at current levels. Among the points
made in the report: 1) Increasing numbers of graduate students
and postdoctoral fellows are failing to find long-term jobs. 2)
In 1973, approximately 11 percent of PhDs still held postdoctoral
or other non-faculty jobs at universities 5 to 6 years after
graduating, or were outside science altogether. By 1995, the
number had risen to 38 percent. 3) The situation has produced a
"crisis in expectation" among young scientists. "The feelings of
disappointment, frustration and even despair are palpable in the
laboratories of academic centers. Further increase in the
competition could discourage the best students from entering the
field. 4) The report recommends that graduate programs should be
required to confront prospective students with the actualities of
their career prospects by providing to prospective students data
on the careers of PhD graduates over the previous 10 years. 5)
Although foreigners accounted for most of the increase in PhD
graduates since 1987, the report suggests this should not lead to
"arbitrary limitations on the number of visas issued for foreign
students."
Meredith Wadman (~Nature~): Jobs crisis sparks call for freeze in
number of PhD students in US.
(Nature 10 Sep 98 395:103)
QY: Meredith Wadman 
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Summary by SCIENCE-WEEK http://scienceweek.com 25Sep98

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Related Background:

ON THE OVERPRODUCTION OF US BIOMEDICAL RESEARCHERS
There are always practical problems concerning the training of
scientists, but two persistent questions are How many? and Where
do they work? Marincola and Solomon (2 installations, US), in a
recent editorial in the journal ~Science~, review the current
problems in the training of biomedical research scientists (and
propose a solution), but the ideas are perhaps just as applicable
to physics and chemistry. The authors make the following points:

1) Although the number of biomedical research trainees in the US
has expanded considerably over the past 20 years, the number of
tenured positions is declining. 2) The average time to obtain a
PhD rose from 4.4 years in the 1970s to 5.6 years in the 1990s.
3) Each principal investigator trains many times the single
scientist required to replace himself or herself. This intrinsic
instability could threaten the profession. 4) Many researchers
perceive that science is thriving at increasing and unacceptable
cost to those being trained. In strictly economic terms, it is in
the interest of senior investigators to maintain the number of
trainees, who work long hours in large numbers for little pay
over many years in return for the chance to develop a satisfying
career. 5) A solution may be to uncouple scientific productivity
from an investigator's ability to attract and employ trainees --
the creation of permanent research positions for scientists who
would neither compete for grants nor train others. They would be
supported through investigators who hold traditional academic
appointments. The authors give as an example the institution of
3-year positions for researchers at the Scripps Institute (US).
The essential idea, then, is the amplification of the number of
already existing non-tenure "research associate" positions, these
positions to be filled by PhDs on a continuing short-term
contract basis. The authors state: "This career track could be
recognized explicitly, legitimized, and nourished to become an
element of the research enterprise." The editorial does not
address the question of how this two-tier structure will satisfy
the career objectives of young scientists who are first-rate, but
because of lack of employment opportunities, are forced into the
second tier.
QY: Elizabeth Marincola 
(Science 31 Jul 98 281:64) (Science-Week 28 Aug 98)


3. EVIDENCE CONCERNING LOCAL EXPANSION RATE OF THE UNIVERSE
The Hubble constant is a measure of the rate of expansion of the
Universe, the average value of velocity of recession divided by
distance. Since the constant is time-dependent, it is more
correctly termed a parameter. It's present value is believed to
be between 50 and 100 km/sec/megaparsec. *Cepheids are variable
stars with periods between 1 and 60 days, the period of variation
for each star related to its luminosity, and this relation making
it possible to use Cepheids as "standard candles" to estimate the
distance of astronomical objects. Both galaxy distances and
velocities are required for the determination of the expansion
rate of the Universe, and an important consideration is that the
radial velocities of galaxies arise not just from this expansion,
but also from random velocity components and large-scale flows.
To reach out to distances dominated by the overall cosmic
expansion, it is necessary to probe large physical scales where
galaxy-galaxy and galaxy-cluster interactions become important.
But accurate distances of nearby galaxies and clusters (commonly
measured using Cepheid variable stars) are required to calibrate
the indirect distance indicators generally used to measure large
scales. Essentially, cosmic distance estimation is a "stepping-
stone" process based on the use of known close distances to
estimate further distances, and the use of these further
distances to estimate still further distances. ... ... B.F.
Madore et al report a Cepheid distance of 18.6 megaparsecs for
the galaxy NGC1365 in Fornax, a cluster of galaxies in the
Southern Hemisphere. The authors deduce a Hubble constant of 70
km/sec/megaparsec from Fornax alone, and a Hubble constant of 73
km/sec/megaparsec from the intervening galaxy flow, each
corrected for gravitational infall into the nearby Virgo cluster.
The authors suggest these values are consistent with the Hubble
constant as measured in the far field using secondary methods.
-----------
B.F. Madore et al (16 authors at 12 installations, US AU UK CA):
A Cepheid distance to the Fornax cluster and the local expansion
rate of the Universe.
(Nature 3 Sep 98 395:47)
QY: Barry F. Madore 
-----------

Text Notes:
... ... *Cepheids: The relation between period of pulsation and
average brightness of Cepheid variable stars was discovered
during 1908-1912 by Henrietta Swan Leavitt (1868-1928), a
graduate of Radcliffe College on the staff of the Harvard
Observatory. Leavitt discovered 2400 variable stars, doubling the
number known in her time. In the early years of stellar
spectroscopy, particularly at the Harvard Astronomical
Observatory, nearly all the data was catalogued and analyzed by
female astronomers, called "computers", who were forbidden
because of their sex to use the telescopes. It is an irony of the
social history of science that the work of such female
astronomers as Henrietta Swan Leavitt and Annie Jump Cannon
(1863-1941) came to be of greater significance than the work of
many of the male astronomers who considered these female
astronomers to be no more than menial assistants. 
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 2Oct98

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

Related Background:

RED GIANT STARS AND CONSTRAINTS ON THE HUBBLE CONSTANT
In cosmology, according to the Hubble law that describes the
expansion of the Universe, a law first proposed by Edwin Hubble
in 1929, the apparent recession velocity of galaxies is
proportional to their distance from the observer, with the
proportionality factor denoted as H(sub0). This proportionality
factor is called the "Hubble constant", but in the *Big Bang
theory it varies with time and is really a parameter rather than
a constant. This important cosmological parameter is usually
measured in units of kilometers per second per megaparsec, which
is identified dimensionally as a variation of velocity with
distance. Assuming the Big Bang origin of the expansion, the
"Hubble time" is defined as the reciprocal of the Hubble
constant, and is the time required for the Universe to expand to
its present state, assuming the Hubble constant has remained
unchanged since the Big Bang. Determination of the Hubble time
has been far from unequivocal, with estimates of the Hubble time
ranging between 9 and 18 billion years, depending on various
measurements, models, assumptions, and so on. In the standard Big
Bang theory, the actual age of the Universe is always less than
the Hubble time, because the expansion was faster in the past.
... ... W.E. Harris et al now present a report of observations of
the brightest *red-giant stars in a *Virgo-cluster galaxy, and
the use of these observations to determine constraints on the
Hubble constant. The authors make the following points: 1) The
nearest large groups of *elliptical galaxies (in the Virgo and
*Fornax clusters) play a central role in determinations of the
Hubble constant, and hence the cosmological rate of expansion.
Because the relative distances between these two clusters and
more remote clusters are well known, absolute distance
determinations to Virgo and Fornax should establish the Hubble
constant for the local universe. 2) In addition, elliptical
galaxies reside predominantly in the cores of galactic clusters,
so distance calibrations for ellipticals should minimize the
uncertainties due to the possibly large extent of the clusters
along the line of sight. 3) The authors suggest that a powerful
and direct way of establishing such distances is to use the
brightest red-giant stars, which have nearly uniform
luminosities. 4) The authors report the direct observation of old
red-giant stars in a *dwarf elliptical galaxy in the Virgo
cluster. They determine a distance to this galaxy, and thus to
the core of the Virgo cluster, of 15 megaparsecs, from which they
estimate a Hubble constant of H(sub0) = 77 +- 8 kilometers per
second per megaparsec. Under assumptions of a *low density
Universe with the simplest cosmology, the authors suggest the age
of the Universe is no more than 12 to 13 billion years.
-----------
W.E. Harris et al (4 authors at 4 installations, CA US):
Constraints on the Hubble constant from observations of the
brightest red-giant stars in a Virgo-cluster galaxy.
(Nature 3 Sep 98 395:45)
QY: William E. Harris 
-----------

Text Notes:
... ... *Big Bang theory: The Big Bang theory is the general
cosmological model that proposes that all matter and radiation in
the universe originated in an explosion at a finite time in the
past.
... ... *red-giant stars: A red giant star is a star in a late
stage of evolution, having exhausted the hydrogen fuel in its
core. It has a surface temperature of less than 4700 degrees
Kelvin and a diameter 10 to 100 times that of the Sun.
... ... *Virgo-cluster galaxy: The Virgo cluster is a giant
irregular cluster of galaxies in the constellation Virgo. It is
the nearest large cluster, and approximately 2500 galaxies have
been identified in it.
... ... *elliptical galaxies: These are galaxies that have no
disc component, the shape varying from almost circular to narrow
ellipses. The stars within elliptical galaxies are predominantly
old stars. Elliptical galaxies display the greatest variation in
mass, ranging down to extreme dwarfs (approximately 10^(6) solar-
masses.
... ... *Fornax: The Fornax system is a dwarf elliptical galaxy
in the Fornax constellation. 
... ... *dwarf elliptical galaxy:  A dwarf galaxy is one that is
unusually faint because of small size or low surface brightness
or both. Dwarf galaxies contain only a few million stars, and
they are usually difficult to observe against foreground stars
because they are almost completely transparent. Dwarf galaxies
apparently make up the bulk of the cosmic population.
... ... *low density Universe: The apparent mean density of
matter in the Universe, as determined from both theory and
observation, is a critical parameter that constrains the geometry
and future history of the Universe, and also the age of the
Universe.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 25Sep98


4. GEOLOGY: 1.4 BILLION-YEAR-OLD UNALTERED COSMIC SPHERULES
Micrometeorites are submillimeter-size particles derived from
asteroids and comets, and they occur in significant quantities in
deep sea sediments and in the ice sheets of Greenland and
Antarctica. The most abundant micrometeorites are cosmic
spherules, which contain nickel-rich spinels (groups of mixed
metal oxides) that were crystallized and oxidized during
atmospheric entry, thus recording the oxygen content in the
uppermost atmosphere. But the use of micrometeorites for
detecting past changes in the flux of incoming extraterrestrial
matter, and as probes of the evolution of the atmosphere, has
been hampered by the fact that most objects with depositional
ages higher than 0.5 million years show severe chemical
alteration. ... ... A. Deutsch et al now report the discovery of
unaltered cosmic spherules in a 1.4 billion year old sandstone
(red bed) from Finland. The authors suggest that red beds, a
common lithology in Earth's history, may contain substantial
unbiased populations of fossil micrometeorites, and that the
study of such populations would allow systematic research on
variations in the micrometeorite flux from the early Proterozoic
era to recent times (a time span of about 2.5 billion years), and
could help to better constrain the time when the atmospheric
oxygen content was raised to its present level.
-----------
A. Deutsch et al (4 authors at 2 installations, DE FI): Unaltered
cosmic spherules in a 1.4-Gyr-old sandstone from Finland.
(Nature 10 Sep 98 395:146)
QY: Alexander Deutsch 
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 2Oct98

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

Related Background:

ACCRETION OF COSMIC SPHERULES MEASURED AT THE SOUTH POLE
Micrometeorites are terrestrially collected extraterrestrial
particles smaller than about 1 mm, and which account for most of
the mass being accreted to the Earth. Compared with meteorites,
micrometeorites more completely represent the Earth-crossing
meteoroid complex, and include fragments of asteroids, comets,
Mars and our Moon, as well as pre-Solar and interstellar grains.
Previous measurements of the flux of micrometeoroids that survive
to the Earth's surface have large uncertainties owing to the
destruction of particles by weathering, inefficiencies in
magnetic collection or separation techniques, low particle
counts, poor age constraint, or highly variable concentrating
processes. ... ... Taylor et al (3 authors at 2 installations,
US) report an attempt to circumvent these problems through the
collection of thousands of well-preserved and dated micrometeor-
ites from the bottom of the South Pole water well that supplies
drinking water for the Scott-Amundsen station. This well is a
5000 m^(3) subsurface water pool. Micrometeorites originally on
the snow surface became incorporated into essentially horizontal
ice layers whose depth-age relationship has been determined from
the stratigraphy of an ice core. As the well melts downward,
micrometeorites released from the ice remain on the bottom of the
water-filled cavity. Using this collection of micrometeorites,
the authors have determined precise estimates of flux and mass
distribution for 50 to 700 micron cosmic spherules (melted
micrometeorites). The authors suggest their results indicate that
about 90% of the incoming mass of submillimeter particles
evaporates during atmospheric entry, and that their results
provide constraints for models describing the survival
probability of micrometeoroids.
QY: James H. Lever (jlever@crrel.usace.army.mil)
(Nature 30 Apr 98 392:899) (Science-Week 22 May 98)


5. MAGNETIC LEVITATION OF ORDINARY OBJECTS
All substances can be influenced by applied magnetic fields.
In terms of magnetic properties, substances are usually divided
into 3 broad categories: 1) Ferromagnetic substances such as
iron, steel, cobalt, and nickel are able to become highly
magnetic in a relatively weak magnetic field. Such substances
contain substantial internal magnetic fields in the absence of an
applied magnetic field. 2) Paramagnetic substances such as liquid
oxygen have a capability to be magnetized which is slightly
greater than that of a vacuum and much less than that of iron.
When placed in a magnetic field, paramagnetic substances are
magnetized parallel to the lines of force of the field to an
extent proportional to the intensity of the field (but not at
extremely low temperatures or extremely high fields). When
removed from an applied magnetic field, the magnetization of
paramagnetic substances returns to zero. 3) *Diamagnetic
substances such as the alkalis and alkaline earth metals, the
halogens, and the noble gases are repelled by magnets and tend to
position themselves at right angles to the magnetic lines of
force. Like paramagnetic substances, when removed from an applied
magnetic field, the magnetization of diamagnetic substances
returns to zero. In the context of this report, "lifting" is
distinguished from "levitation", with levitation referring to
stable floating in an applied magnetic field. ... ... In a review
of the behavior of diamagnetic materials in laboratory magnetic
fields, Andrey Geim makes the following points: 1) All materials
can be lifted by magnetic fields that are currently standard. 2)
Due to the readjustment of electron orbits in a magnetic field,
all objects exhibit diamagnetism, which determines the lowest
possible limit of their magnetic response... Fields of
approximately 10 *tesla are sufficient to lift practically any
substance. 2) Magnetic fields strong enough to lift diamagnetic
materials became available during the mid 20th century, and
*superconductors were first levitated in 1947. It took 50 years
to rediscover the levitation of conventional room-temperature
diamagnetic materials. In 1991, Beaugnon and Tournier
magnetically lifted water and a number of organic substances.
Other researchers soon levitated liquid hydrogen, helium, and
frog eggs. The author's research group at the University of
Nijmegen (NL) has levitated practically everything at hand, "from
pieces of cheese and pizza to living creatures including frogs
and a mouse." (The article includes a photograph of a levitated
live frog in the bore of a 20 T magnet, the frog reported to
exhibit no adverse effects from exposure to the magnetic field.)
The magnetic fields used in these experiments have been available
for decades. 3) In contrast to diamagnetic substances,
paramagnetic substances cannot levitate. Only diamagnetic
substances can flaunt *Earnshaw's theorem, which states that no
stationary object made of charges, magnets, and masses can be
held in space by any fixed combination of electric, magnetic, and
gravitational forces. Diamagnetism involves electron motion
around nuclei, and thus is not a fixed configuration as required
by the theorem. 4) A diamagnetic substance can levitate only
close to an inflection point of the vertical component of the
magnetic field. This is a purely geometric condition independent
of the field strength. 5) The author suggests an example of the
exploitation of the diamagnetic force: the direction of growth of
germinating seeds, which ordinarily depends on gravity, can in
the absence of gravity (e.g., in a space ship) be determined by a
small permanent magnet (O.A. Kuznetsov and K.H. Hasenstein,
_Planta_ 1996 198:87).
-----------
A. Geim (University of Nijmegen, NL): Everyone's magnetism.
(Physics Today September 1998)
QY: Andrey Geim, University of Nijmegen, NL.
-----------

Text Notes:
... ... *Diamagnetic substances: Diamagnetism was discovered by
Michael Faraday in 1846.
... ... *tesla: International System unit of magnetic flux
density. 1 tesla = 1 weber per square centimeter.
... ... *superconductors: Superconductivity is a property of many
metals, alloys, and chemical compounds at temperatures near
absolute zero, at which temperatures their electrical resistivity
vanishes and they become strongly diamagnetic.
... ... *Earnshaw's theorem: The classic statement of this
theorem is that a charge cannot be held in stable equilibrium in
an electric field under the influence of electric forces alone.
The theorem as given in the text by Geim is a recent
reformulation by Michael Berry (M.V. Berry and A.K. Geim, Eur. J.
Phys. 1997 18:307)
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 2Oct98


6. CHEMICAL ALTERATION OF SINGLE CELLS WITH ELECTROPORATION
Although many high-resolution techniques exist to detect, image,
and analyze the contents of single cells and subcellular
organelles, few methods exist to control and manipulate the
biochemical nature of these compartments. ... ... J. Lundqvist et
al now report a technique for the selective chemical and
biological manipulation of the contents of individual living
cells, the technique based on the electric field-induced
permeabilization (*electroporation: the formation of pores by
electric means) in biological membranes using a low-voltage pulse
generator and microelectrodes. The authors report that a
spatially highly focused electric field allows the introduction
of polar cell-impermeant solutes such as fluorescent dyes,
fluorogenic reagents, and DNA into single cells and intracellular
compartments. The high spatial resolution of the technique allows
for design of cellular network constructions in which cells in
close contact with each other can be made to possess different
biochemical, biophysical, and morphological properties. The
electroporation with subcellular spatial resolution is achieved
by applying the electric field through carbon fiber
microelectrodes (approximately 5 microns in diameter, the carbon
fiber fixed to the tip of a potassium chloride-filled glass
micropipette), with a spacing between the electrodes typically 20
microns or less. 
-----------
J. Lundqvist et al (6 authors at 2 installations, SE): Altering
the biochemical state of individual cultured cells and organelles
with ultramicroelectrodes.
(Proc. Natl. Acad. Sci. US 1 Sep 98 95:10356)
QY: Owe Orwar 
-----------

Text Notes:
... ... *electroporation: Conventional electroporation techniques
using high voltage generators generally involve batch-mode
electroporation of the membranes of millions of cells
simultaneously. Methods also exist for electroporation of small
numbers of cells in suspension or small numbers of cells adhering
to a substrate. The focus of this report is the electroporation
of individual cells and parts of cells, and the report includes
photographs of a single cell in a small group of cells 
electroporated to incorporate fluorescein. Other photographs in
the paper present evidence of electroporation and dye
incorporation of organelles in single cells.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 2Oct98


7. MOLECULAR BIOLOGY: APOPTOSIS, MITOCHONDRIA, AND CASPASES
Apoptosis (programmed cell death) is a rapid and specific process
involving the production of a number of enzymes in the cell
programmed to be destroyed. This programmed destruction is not
always harmful, or always the result of cellular damage of one
sort or another. In humans, for example, the lack of webbing
between fingers and toes is a result of apoptosis of cells of
webbing tissue occurring during embryological development, the
apoptosis in this case being a normal part of the larger
embryological program. In the mature organism, apoptosis is the
usual method of removing damaged cells after these cells are
recognized to be damaged by one mechanism or another. It is known
that normal cells carry an apoptosis receptor on their surfaces,
called CD95, and that when this surface receptor is cross-linked
by its specific ligand, this triggers the sequence of events
known as apoptosis. In the apoptosis sequence, certain
*proteolytic enzymes inside the cell are activated, and in
addition a variety of lipids that cause cell dysfunction are
synthesized. ... ... D.R. Green and J.C. Reed review the
involvement of *mitochondria with apoptosis in *metazoan cells,
and the authors make the following points: 1) The current
consensus among biologists is that approximately 2 billion years
ago the cells destined to become the ancestors of all *eukaryotes
entered into a partnership with an ancestor of today's *purple
bacteria, an ancestor that subsequently became the mitochondria
of today. 2) It has been hypothesized by several investigators
that the *endosymbiotic origins of mitochondria and the evolution
of aerobic metabolism in eukaryotes formed the basis for the
evolution of active cell death, which in metazoans is manifested
predominantly as apoptosis. Central roles for mitochondria as the
orchestrators  of apoptosis have been firmly established in many
systems. 3) In recent years it has become apparent that the
effectors of apoptosis are a family of intracellular proteases
known as caspases, although inhibiting these enzymes does not
always prevent apoptosis. 4) At least 3 general mechanisms have
been proposed for the involvement of mitochondria in the control
of cell life and death: a) disruption of *electron transport,
*oxidative phosphorylation, and adenosine triphosphate (ATP)
production; b) release of proteins that trigger activation of the
caspases family of proteases; c) alteration of cellular *redox
potentials. 5) In many apoptosis scenarios, the mitochondrial
inner electrical transmembrane potential collapses, indicating
the opening of large conductance channels through the inner
membrane. In contrast, certain stimuli can induce rupture of the
outer membrane of mitochondria and release of caspase-activation
proteins. The authors conclude: "Perhaps a few hundred million
years ago, either convergent or divergent evolutionary processes
allowed the ... fundamental framework for bacterial warfare to be
incorporated into the cell death mechanisms used by animal cells,
thereby establishing mitochondria as important participants not
only in animal cell life but also in active cell death." ... ...
In a companion and contiguous review of caspases and apoptosis,
N.A. Thornberry and Y. Lazebnik point out the following: 1)
Proteolysis is irreversible, which implies that regulation of
proteases is limited to control of their activity and
availability of substrate -- the only known way of "correcting" a
cleaved protein is to make it afresh. 2) Most proteases are
synthesized as precursors that have little if any catalytic
activity. The precursor is usually converted to the active enzyme
by proteolytic processing mediated either by another protease or
by autocatalysis. Thus large amounts of precursor can be
accumulated in advance and activated on demand. 3) Proteases can
regulate their own activation, resulting in an exponential rate
of activation. 4) Where there are proteases there are inhibitors,
and these inhibitors regulate the concentration of active
protease in the cell. 5) Proteolytic reactions can be specific,
determined by a combination of primary, secondary, or tertiary
structures of protein substrates. Proteolysis that governs
critical biological processes such as the cell cycle or cell
death is highly specific and involves a restricted set of
substrates. 6) The various caspases share similarities in amino
acid sequence, structure, and substrate specificity. 7) Caspases
are among the most specific of proteases with an unusual and
absolute requirement for cleavage after aspartic acid and
recognition of at least 4 amino acids terminal to the cleavage
site. 8) The strict specificity of caspases is consistent with
the observation that apoptosis is not accompanied by
indiscriminate protein digestion, but rather a select set of
proteins is cleaved in a coordinated manner, usually at a single
site, resulting in a loss or change in function. 9) Apoptotic
events include DNA fragmentation, *chromatin condensation,
*membrane blebbing, cell shrinkage, and disassembly into
membrane-enclosed vesicles (apoptotic bodies). In vivo, this
process culminates with the engulfment of apoptotic bodies by
other cells, preventing complications that would result from a
release of intracellular contents. In apoptosis, these changes
occur in a predictable reproducible sequence and can be completed
with 30 to 60 minutes. The authors conclude: "Substantial
progress has been made in understanding the structural and
catalytic properties of active caspases and their contribution to
apoptosis. The goal for future research is to understand the
regulation of these enzymes. This should facilitate efforts to
rationally manipulate the apoptotic machinery for therapeutic
gain."
-----------
D.R. Green and J.C. Reed (2 installations, US): Mitochondria and
apoptosis.
(Science 28 Aug 98 281:1309)
QY: Douglas R. Green, La Jolla Institute for Allergy and
Immunology, 10355 Science Center Drive, San Diego, CA 92121 US.
N.A. Thornberry and Y. Lazebnik (2 installations, US): Caspases:
enemies within.
(Science 28 Aug 98 281:1312)
QY: Nancy A. Thornberry, Merck Research Laboratories, Rahway, NJ
07065 US.
-----------

Text Notes:
... ... *proteolytic enzymes: These enzymes, also called
"proteases", split proteins and thereby degrade them. The enzymes
catalyze the hydrolysis of peptide bonds, fragmenting proteins
into polypeptide chains, and fragmenting polypeptide chains into
constituent amino acids. Sometimes proteolytic enzymes and
proteases are distinguished, with the term "proteases" reserved
for proteolytic enzymes with high specificity for peptide bonds
between particular amino acids.
... ... *mitochondria: Mitochondria are double-membrane enclosed
organelles of cells that are involved with several important
biochemical pathways, including electron transport and oxidative
metabolism, and across the membrane of the mitochondrion there
exists a potential difference apparently due primarily to a
concentration gradient of hydrogen ions. Various types of
eukaryotic cells may contain from a few to several thousand
mitochondria in each cell type. The mitochondria are relatively
large cylindrical structures up to 10 microns long and up to 2
microns in diameter.
... ... *metazoan cells: Metazoans are multicellular animals.
... ... *eukaryotes: Cells (and organisms consisting of such
cells) that contain intracellular membrane-bound compartments
such as a nucleus (membrane-bound "organelles").
... ... *purple bacteria: Specifically, any of the various
photosynthetic bacteria that contain bacteriochlorophyll, and are
thus distinguished by purplish or reddish-brown pigments. But
the
term "purple bacteria" is sometimes used as a synonym for the
phylum Proteobacteria, a general category comprising a large
number of diverse forms.
... ... *endosymbiotic: Endosymbiosis is an arrangement in which
one organism lives inside another organism, but the term is
usually restricted to arrangements of mutual benefit, thus not
including parasite-host relationships. A number of eukaryotic
cell organelles (including mitochondria) are believed to have
originated from endosymbiotic relationships between eukaryotic
cells and simpler cells.
... ... *electron transport: Refers to a sequence of steps in the
final stage of the aerobic respiration biochemical pathway in
which high energy electrons are effectively passed through a
series of membrane-bound carrier molecules to support a proton
gradient involved in energy storage. The term "transport" here
refers essentially to a chemical flow diagram and not necessarily
to an actual spatial translocation of electrons.
... ... *oxidative phosphorylation: Production of ATP during
aerobic respiration. It takes place in the mitochondria of
eukaryotic cells and requires molecular oxygen as a terminal
electron acceptor.
... ... *redox potentials: Chemical potentials in a chemical
reaction involving the simultaneous reduction and oxidation of
two compounds by a transfer of electrons between them.
... ... *chromatin: The entire complex of a eukaryotic
chromosome, including DNA, chromosomal proteins, and chromosomal
RNA.
... ... *membrane blebbing: Refers to the macroscopic blistering
of the surfaces of cells when they die under certain conditions.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 2Oct98

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

Related Background:

EVIDENCE THAT BREAST CANCER GENE IS APOPTOSIS COACTIVATOR
In molecular biology, the term "transcription" refers to the
sequence of biochemical events producing the conversion of DNA
code to RNA code. Apoptosis is programmed cell death produced by
control mechanisms designed to destroy defective cells or cells
that must be discarded in the process of tissue differentiation.
Mutations of the gene {BRCA1} have been linked to 45% of the
cases of familial breast cancer, and to 80% to 90% of families
with both breast and ovarian cancer. ... ... Now Ouchi et al (5
authors at 4 installations, US) report that {BRCA1} stimulates
artificial and genomic entities that contain elements responsive
to the tumor suppressor protein p53, which is known to be
involved in apoptosis. The authors suggest their findings
indicate the gene {BRCA1} is involved in transcriptional
regulation and has a function as a p53 coactivator.
QY: Hidesaburo Hanafusa (saburo@rockvax.rockefeller.edu)
(Proc. Natl. Acad. Sci. US 3 Mar 98)

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

Related Background:

BCL-2 PREVENTS APOPTOSIS BY PROTON FLUX REGULATION
Mitochondria are double-membrane enclosed organelles of cells
that are involved with several important biochemical pathways,
including electron transport and oxidative metabolism, and across
the membrane of the mitochondrion there exists a potential
difference apparently due primarily to a concentration gradient
of hydrogen ions. Biological cells are programmed to self-
destruct under certain condition, for example, when there is a
serious genome replication error, and the self-destruct sequence
is called "apoptosis". Cancer cells, which are derived from
normal cells whose genomes have undergone certain specific
mutations, require for their proliferation the activation in
their genome of genes that prevent apoptosis. The gene 
has been identified as such a gene, and is called a "proto-
oncogene". This gene expresses the protein Bcl-2, and this
protein has been shown to prevent the loss of the mitochondrial
membrane potential, one of the events involved in apoptosis.
... ... Shimizu et al (8 authors at 2 installations, JP FR)
report that the protein Bcl-2 prevents both the loss of the
mitochondrial membrane potential (depolarization) and the
permeability transition induced by various reagents (e.g.,
Ca(sup2+), H(sub2)O(sub2), and tert-butyl hydroperoxide). The
authors suggest their results indicate Bcl-2 maintains the
mitochondrial membrane potential by enhancing H(sup+) efflux in
the presence of stimuli that induce depolarization.
QY: Yoshihide Tsujimoto 
(Proc. Natl. Acad. Sci. US 17 Feb 98)

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

Related Background:

APOPTOSIS: RELEASE OF CYTOCHROME C IS NOT SUFFICIENT
Transfection is the uptake of exogenous (foreign) DNA fragments
in solution directly into animals cells in laboratory culture,
and is one method of introducing foreign genes into cells. Bcl-2
is a protein that interferes with the activation of caspases by
preventing the release of cytochrome c, and Bax is a homolog of
Bcl-2 that promotes apoptosis. The term "membrane blebbing"
refers to the macroscopic blistering of the surfaces of cells
when they die under certain conditions. ... ... Rosse et al (8
authors at 2 installations, CH AT) report that in cells
transiently transfected with the gene , the protein Bax
localizes to mitochondria and induces the release of cytochrome
c, activation of caspase-3, membrane blebbing, nuclear fragment-
ation, and cell death. It was also found that cells overexpress-
ing both proteins Bcl-2 and Bax show no signs of caspase activ-
ation and survive with significant amounts of cytochrome c in the
cytoplasm. The authors suggest their findings indicate Bcl-2 can
interfere with Bax-induced apoptosis downstream and independent
of cytochrome c release.
QY: Christoph Borner 
(Nature 29 Jan 98)

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

Related Background:

INDUCTION OF APOPTOSIS BY INJECTED CYTOCHROME C
The cytochromes, categorized as hemoproteins with differing
porphyrin groups, are widely distributed respiratory (oxygen-
utilizing) catalysts involved in the electron transport chain of
living cells. They do not combine with substrates, but alternate
between Fe(2+) and Fe(3+) states. There are various cytochromes,
with cytochrome c present in the greatest amounts, and most
importantly in the mitochondria of eukaryotic cells. Apoptosis is
programmed cell death produced by control mechanisms designed to
destroy defective cells or cells whose destruction is necessary
for the specialization of tissues. Adrenocortical tumor cells are
tumor cells arising from the cortex of the adrenal gland(s);
epithelial cells are cells lining the interior of body cavities
or exposed surfaces of the body; fibroblasts are a type of
connective tissue cell secreting structural proteins (e.g.,
collagen); and promyelocytic leukemia cells are large uninuclear
cells circulating in the blood of persons with leukemia of a type
of blood cell called myelocytes (bone marrow granulocytes).
Caspase is a type of protease, an enzyme that degrades protein by
hydrolysis, and it has been implicated in apoptosis. Apparently,
when cells are exposed to stimuli that trigger apoptosis,
cytochrome c is rapidly released from mitochondria into the
cytoplasm, and there cytochrome c activates caspases that begin
the destruction of the cell. ... ... Zhivotovsky et al (4 authors
at 2 installations, SE NO) report that microinjection into cells
of cytochrome c activates apoptosis, the effect seen in various
cell types, including adrenocortical tumor cells, normal rat
kidney epithelial cells, mouse embryonic fibroblasts, and rat
promyelocytic leukemia cells, and that the effect is caspase-
dependent. QY: Stenn Orrenius 
(Nature 29 Jan 98)

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

Related Background:

A CASPASE INVOLVEMENT IN OOGENESIS APOPTOSIS
Oocytes are egg cells, and in invertebrates, "nurse cells" are
accessory cells connected to oocytes by cytoplasmic bridges that
allow nutrients to be directly transferred to the oocyte. The
cytoskeleton of biological cells is the quasi-rigid matrix that
among other things determines cell shape. Proteases are a class
of enzymes that hydrolyze proteins, splitting them into various
groups of subunits, with the sites of hydrolysis dependent on the
particular enzyme and the protein substrate, and a caspase is a
type of protease. Apoptosis is programmed cell death produced by
control mechanisms designed to destroy defective cells, or cells
that must necessarily be discarded in the embryological develop-
ment of tissues. ... ... McCall and Stellar (Massachusetts
Instit. of Technol., US) report that loss of function of the
Drosophila gene , which encodes a caspase, causes female
sterility by inhibiting the transfer of cytoplasm to oocytes by
nurse cells, the nurse cells being apparently defective in the
cytoskeletal reorganization and nuclear breakdown that normally
accompany this process. The authors suggest their results
demonstrate that scheduled apoptosis of nurse cells is a
necessary event in oocyte development.
QY: Hermann Steller, Mass. Inst. of Tech. 617-253-4738.
(Science 9 Jan 98)

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

Related Background:

PROTEASES AS MEDIATORS OF APOPTOSIS
Proteases are a class of enzymes that hydrolyze proteins,
splitting them into various groups of subunits, with the sites of
hydrolysis dependent on the particular enzyme and the protein
substrate. Actin is a structural protein present in all cells 
as a constituent of the cell cytoskeleton, and gelsolin is a
protein that breaks actin filaments and causes a gel-sol
conversion -- a conversion of a gelatin-like system to a solution
(liquid) system. This type of conversion is ordinary in certain
cell types under certain conditions, but it is also seen in
apoptosis (programmed cell death) when the cytoskeleton is
destroyed and the cytoplasm liquified. Srinivas Kothakota et al
(11 authors at 3 installations, US) report that the protein
gelsolin is the primary substrate for the caspase-3 protease
family that has been implicated in apoptosis. Gelsolin cleavage
products cause multiple cell types to round up, detach from the
cell culture plate, and undergo nuclear fragmentation. Cells
isolated from genetically engineered mice lacking gelsolin showed
marked delays in apoptosis onset following apoptosis induction,
while wild-type cells did not show these delays. The authors
suggest that cleaved gelsolin may be one of the physiological
effectors that produce morphological changes during apoptosis.
QY: David J. Kwiatkowski 
(Science 10 Oct 97)

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

Related Background:

EVIDENCE FOR RECEPTOR DECOYS IN APOPTOSIS
In the previous report, we mentioned tumor suppressor genes,
sequences of DNA that code for proteins that prevent or inhibit
the growth of tumors. One of these genes codes for a protein
called p53, and evidently the function of this protein, closely
studied in many laboratories, is to trigger an internal suicide
program after the DNA of a cell has been damaged by drugs or
radiation. The process is called apoptosis -- programmed cell
death -- and what is characteristic of many types of cancer cells
is that the gene that codes for p53 has been damaged, the damaged
gene replicated from one generation of cancer cell to another,
and in the resulting absence of the protein p53 no apoptosis
occurs. In other words, the program whose function is to elim-
inate cells with corrupted DNA has itself been corrupted, and an
important fail-safe mechanism has been destroyed. There are other
endogenous cytotoxic proteins beside p53. One of them is called
TRAIL (also called Apo2L), and it is quite remarkable in that it
apparently induces apoptosis of many transformed cancer cell
lines but not of normal cells, even though its receptor is
evidently present in both cell types. Reports this week by Guohua
Pan et al (University of Michigan, US; Human Genome Sciences,
Rockville MD US) and James P. Sheridan et al (Genentech, San
Francisco CA US) indicate that normal cells contain a decoy
receptor for TRAIL, the decoy receptor not activating apoptosis,
while cancer cells susceptible to TRAIL do not contain the decoy
receptor, only the receptor that does activate apoptosis. Why
this difference in receptors should exist, given the evolution
pressures on cancer cells, is a mystery. But there is some hope
now that if the complexities of these "death-domain" receptors
can be unraveled, means may be found to use the TRAIL receptors
in cancer cells to kill them.
QY: V. M. Dixit ; A. Ashkenazi 
(Science 8 Aug 97)

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

MECHANISM OF ACTION OF TUMOR SUPPRESSOR PROTEIN P53
Tumor suppressor genes apparently code for proteins that either
prevent cell division or provoke cell death, and since the
molecular mechanisms involved in these events are of great
importance in current efforts in cancer research, all the
elements in the sequences are of significance. Apoptosis is the
name given to the programmed cell death provoked by the proteins
expressed by tumor suppressor genes. Kornelia Polyak et al (Johns
Hopkins University, US) have investigated the genes whose
transcription is activated by protein p53, perhaps the most
important tumor suppressor protein, and they present a model for
the mechanism of apoptosis produced by this protein. The model
involves the transcriptional induction of redox related genes,
the formation of reactive oxygen species, and finally the
oxidative degradation of mitochondrial components, this sequence
then culminating in the death of the cell.
QY: Kenneth W. Kinzler, Johns Hopkins Oncology Cntr, 424 N. Bond
St., Baltimore MD 21241 US
(Nature 18 Sep 97)


8. 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 
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 
-----------

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:

FUNCTIONAL ANATOMY OF HUMAN MUSIC PROCESSING
The existence of special perceptuo-motor skills in certain
individuals presents many puzzling questions for the cognitive
neurosciences. One such ability whose cerebral substrate remains
essentially unknown is absolute pitch (also called "perfect
pitch"), a relatively rare ability that refers to a long-term
internal representation for the pitch of tones in the musical
scale, typically manifested behaviorally by the ability to
identify by the name of the musical note the pitch of any sound
without reference to another sound, or by the ability to produce
a given musical tone on demand. In contrast, relative pitch,
which is well-developed among most trained musicians, refers to
the ability to make pitch judgments about the relation between
notes, such as within a musical interval. The term "functional
brain imaging" refers to a number of different techniques for
mapping activity in the brain in response to external stimuli or
during sensory, perceptual, or cognitive events. Positron
emission tomography 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. Magnetic resonance
imaging is a technique involving images produced by mobile
protons of a tissue excited by the application of a magnetic
field, and when used in functional cerebral imaging, the basis of
the technique is that it images very small metabolic, blood-flow,
and perfusion-diffusion changes in vivo, in real time, and with
no risk to the subject. ... ... Zatorre et al (5 authors at
McGill University, CA) report a study of the neural basis of
human absolute pitch using both structural and functional brain
imaging techniques (magnetic resonance imaging and positron
emission tomography). Although there were some localization
differences between absolute pitch possessors and control non-
absolute-pitch musicians when responding to musical tones, the
results as a whole bring the authors to suggest that absolute
pitch may not be associated with a unique pattern of cerebral
activity, but rather may depend on the recruitment of a
specialized network involved in the retrieval and manipulation of
verbal-tonal associations.
QY: Robert J. Zatorre (md37@musica.mcgill.ca)
(Proc. Natl. Acad. Sci. US 17 Mar 98 v95:p3172)
(Science-Week 24 Apr 98)

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

Related Background:

ON DYSLEXIA AND FUNCTIONAL DISRUPTION IN BRAIN ORGANIZATION
Dyslexia is impaired reading ability when the reading competence
is below that expected from the individual's general intelligence
and there is no impairment of vision. It has been proposed that
dyslexic children and adults lack phonologic awareness, an
awareness that strings of letters (orthography) are connected to
corresponding units of speech (phonologic constituents) that they
represent. In biology, magnetic resonance imaging is a technique
involving images produced by mobile protons of a tissue excited
by the application of a magnetic field, and when used in funct-
ional cerebral imaging, the basis of the technique is that it
images very small metabolic, blood-flow, and perfusion-diffusion
changes in vivo, in real time, and with no risk to the subject,
with the essential idea of mapping activity in the brain in
response to external stimuli or during sensory, perceptual, or
cognitive events. ... ... Now Shaywitz et al (15 authors at 2
installations, US) report a study to find the location and extent
of the functional disruption in neural systems that underlies
dyslexia. Functional magnetic resonance imaging was used to
compare brain activation patterns in dyslexic and nonimpaired
subjects as they performed tasks that made progressively greater
demands on phonologic analysis. Brain activation patterns
differed significantly between the groups, with dyslexic readers
showing underactivation in certain specific brain areas and
overactivation in other specific brain areas. The authors suggest
their results support a conclusion that the impairment in
dyslexia is phonologic and that brain activation patterns may
provide a neural signature for this impairment.
QY: Sally E. Shaywitz (sally.shaywitz@yale.edu)
(Proc. Natl. Acad. Sci. US 3 Mar 98)

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

Related Background:

SPATIAL WORKING MEMORY LOCALIZED IN HUMAN FRONTAL CORTEX
Magnetic resonance imaging is a technique involving images
produced by mobile protons of a tissue excited by the application
of a magnetic field, and when used in functional cerebral
imaging, the basis of the technique is that it images very small
metabolic, blood-flow, and perfusion-diffusion changes in vivo,
in real time, and with no risk to the subject, with the essential
idea of mapping activity in the brain in response to external
stimuli or during sensory, perceptual, or cognitive events. The
brain-anatomical term "superior frontal sulcus" refers to a
fissure on the superior frontal surface of each frontal lobe. In
this report, "working memory" is the process of maintaining an
active representation of information so that it is available for
use, and "spatial working memory" refers to working memory
involved with spatial memory tasks (remembering locations of
briefly displayed objects or images). ... ... Courtney et al (5
authors at National Institutes of Health, US), using functional
magnetic resonance imaging in humans, report an area in the
superior frontal sulcus specialized for spatial working memory.
The authors suggest that localization of the area in a more
superior and posterior region in the human brain than in the
monkey brain may explain why it has not been recognized
previously.
QY: Susan M. Courtney 
(Science 27 Feb 98)

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

Related Background:

ON THE HISTORY AND APPLICATIONS OF FUNCTIONAL BRAIN IMAGING
The term "functional brain imaging" refers to a number of
different techniques for mapping activity in the brain in
response to external stimuli or during sensory, perceptual, or
cognitive events. Positron emission tomography 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. Fluoro-
deoxyglucose 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 consump-
tion. Magnetic resonance imaging is a technique involving images
produced by mobile protons of a tissue excited by the application
of a magnetic field, and when used in functional cerebral
imaging, the basis of the technique is that it images very small
metabolic, blood-flow, and perfusion-diffusion changes in vivo,
in real time, and with no risk to the subject.
... ... M. Raichle (Washington Univ. School f Medicine, US)
reviews the new techniques of functional brain imaging: positron
emission tomography and magnetic resonance imaging. The author
suggests these tools provide the potential to provide unparallel-
ed insight into some of the most important scientific, medical,
and social questions facing mankind, and that understanding these
tools should be a high priority.
QY: Marcus E. Raichle 
(Proc. Natl. Acad. Sci. US 3 Feb 98)