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.

May 25, 2001 -- Vol. 5 Number 21

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It is theory which decides what we can observe.
-- Albert Einstein (1879-1955)

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Section 1
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Contents of this Issue (Full reports in Section 2):

1. GEOPHYSICS: ON SUPERCHRONS
Geomagnetic polarity reversal is an inversion of the
geomagnetic dipole. Unlike the nearly constant periods of the
solar magnetic cycle, geomagnetic polarity intervals evidently
vary from a few tens of thousands of years to "superchrons" of
the order of tens of millions of years. New data suggests
superchrons may be related to geomagnetic field intensity.

2. MATERIALS SCIENCE: MAGNESIUM DIBORIDE AS A SUPERCONDUCTOR
The recent discovery of high-temperature superconductivity in the
common compound magnesium diboride caught researchers around the
world by surprise. Many reports on the superconducting properties
of magnesium diboride have now been published, and considerable
excitement is still evident in the superconductor research
community.

3. APPLIED MATHEMATICS: ON COMPUTING MORPHOGENESIS
The slime mold morphogenesis cycle is one of the great puzzles of
biology, and a simulation produced by a new mathematical model
will no doubt startle many biologists. This new approach provides
evidence that computer modeling involving recognized subcellular
dynamic entities may soon be used to explain specific tissue
development and tissue morphology. The implications for both
basic and medical biology are profound.

4. CELL BIOLOGY: ION CHANNEL PROTEINS AND CALCIUM CHANNELS
Ion channels in biological membranes are highly regulated, linked
to key cellular processes, and during the past two decades, an
intensive effort in many laboratories has led to identification
of the proteins of some ion channels. A new calcium ion channel
protein has now been identified.

5. BIOCHEMISTRY: ON PROTEIN FOLDS AS NATURAL FORMS
In biological systems, proteins assume various complex
high-order configurations ("folding"), and it is these
configurations that usually determine the roles of proteins as
biochemical entities in the biological system. Many biochemists
now consider protein folds as "natural forms", intrinsic parts of
the natural order of biological matter.

6. HISTORY OF BIOLOGY: ON THE DISCOVERY OF HEMATOBLASTS
Hematoblasts, the primary stem cells of all blood cell types,
were first discovered and named in the 1870s, with credit for the
discovery usually given to the noted French hematologist Georges
Hayem (1841-1933) (sometimes called the "father of hematology").
But now there is evidence that Hayem was not the discoverer of
hematoblasts, and that Hayem in fact may have lifted the name
"hematoblast" from an earlier paper by someone else.

7. IN FOCUS: ON THE MYTH OF THE MIRACLE OF GENIUS
What works in the mind of genius when profound conceptual
discoveries are made in science? The idea of an epiphany
experience as the basis of a conceptual breakthrough by a genius
mind is often based on mythical anecdotes.

8. FROM THE SCIENCEWEEK ARCHIVE:
ASTRONOMY: ON THE EFFECTS OF ASTEROID-EARTH IMPACTS
During the past several years, there has been much media
attention devoted to the prospect of an asteroid impacting Earth.
But if we do detect a large asteroid on a collision-course with
Earth, it is not yet clear what we can do about it with our
present technology except perhaps engineer a nuclear missile hit
to deflect it.


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Section 2
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1. GEOPHYSICS: ON SUPERCHRONS
     The earliest demonstration that the geomagnetic field of the
Earth changed polarity in the past was provided by P. David and
R. Brunhes, who in 1904-1906 described the magnetic properties of
young lava flows in the Massif Central region of France. They
found that clays baked by the lava flows had the same direction
of *remanent magnetization as the lavas, and that when the
magnetization direction in the lava was opposite to that of the
present-day field, the same was the case in the baked clay. They
interpreted the opposite polarities as evidence that the
geomagnetic field can reverse its polarity.
     M. Matuyama (1929) was the first to associate the polarity
of remanent magnetization in lavas with their age as determined
*stratigraphically. Matuyama reported finding young *Quaternary
lavas with magnetization directions close to the present-day
field direction, whereas the directions of older Quaternary and
*Pleistocene lavas were clustered about an *antipodal direction.
He also found that one of three samples of *Miocene *basalt was
magnetized oppositely to the other two. Matuyama's interpretation
was that geomagnetic polarity had changed several times during
the *Late Tertiary time-frame.
     Although generally accepted today, the idea that Earth's
geomagnetic polarity could change was controversial in the early
part of this century, and for many years skeptics sought
alternative interpretations of the data. Alternative
explanations, however, have not been successful, and the
phenomenon is now considered real and is studied as a special
branch of geophysics.
     Geomagnetic polarity reversal is an inversion of the
*geomagnetic dipole. It is a global event, experienced
simultaneously all over the Earth, and such reversals, apart from
their intrinsic interest, provide a convenient means of
stratigraphic correlations and stratigraphic dating. The
paleomagnetic record indicates that the dipolar part of the
Earth's magnetic field, which is the dominant structure of the
geomagnetic field outside the *core, has reversed its polarity
several hundred times during the past 160 million years. The
reversal durations (i.e., the periods during which the reversals
are accomplished) are relatively short (typically 1000 to 6000
years), compared with the constant polarity intervals between
reversals. Another feature of the reversal period is that the
intensity of the magnetic field apparently decreases
significantly during this time-frame.
     Unlike the nearly constant periods of the solar magnetic
cycle, geomagnetic polarity intervals evidently vary from a few
tens of thousands of years to "superchrons" of the order of tens
of millions of years. The duration of a superchron is roughly the
timescale required for significant changes in the thermal
structure of the Earth's *mantle to occur as a result of
*subduction of *tectonic plates and mantle convection, and this
observation and some noted correlations between *plate tectonics,
geomagnetic field intensity, and reversal frequency have led to
speculations that structural changes in the mantle may be
influencing convection and magnetic field generation in the fluid
outer core (the "geodynamo"). In particular, it has been
suggested that changes in both the total heat flow and the
pattern of heat flux over the core-mantle boundary may affect the
geodynamo. Other explanations (see below) have also been
proposed.
... ... S.K. Banerjee (University of Minnesota, US) presents a
commentary on recent research on paleomagnetic reversals (J.A.
Tarduno et al: Science 291:1779 2001), with the author (Banerjee)
making the following points:
     1) The author points out that the Earth's magnetic field
reverses a few times within every million years at random
intervals, the reversals apparently the result of positive
feedbacks to magnetohydrodynamic instabilities with Earth's
liquid iron core. Occasionally, however, the dynamo mechanism in
Earth's liquid iron core apparently stops its random dipole field
reversals, and for 30 to 50 million years the core maintains
either "normal" polarity (the present polarity) or the reversed
state (in which a compass would point south). At least two such
"superchron" periods have been identified to have occurred in the
recent geological past: a) between 118 and 83 million years ago
(the *Cretaceous superchron), the field maintained constant
normal polarity, and b) the field remained reversed from 312 to
262 million years ago. The author asks: Why did the random
dipolar reversal suddenly stop during these periods, and what
made the random reversals start again?
     2) The author points out that the answer to this question
requires accurate data of geomagnetic field behavior during a
superchron in order to devise and test models of geomagnetic
dynamo behavior that could cause it. Tarduno et al report the
latest in a series of innovative attempts to accurately determine
the magnitude of the magnetic field at Earth's surface and the
virtual dipole moment at Earth's center during the Cretaceous
superchron. Unlike the low values found for the virtual dipole
moment by previous authors, Tarduno et al find that during the
Cretaceous superchron the time-averaged virtual dipole moment was
twice as high as the average for the past 160 million years and
50 percent higher than today. The Tarduno et al study involved
149 millimeter-sized single crystals of *plagioclase feldspar,
the crystals extracted from 8 independent lava flows that erupted
at different times between 113 and 115 million years ago. The
geologic site was the Rajmahal volcanic field near the Bihar/West
Bengal state boundary in eastern India. Tarduno et al suggest
that their data support a correlation between intervals of low
geomagnetic reversal frequency and high geomagnetic field
strength.
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S.K. Banerjee: When the compass stopped reversing its poles.
(Science 2 Mar 01 291:1714)
QY: Subir K. Banerjee: banerjee@umn.edu
-----------
Text Notes:
... ... *remanent magnetization: Remanent magnetism is that
component of a rock's magnetization whose direction is fixed
relative to the rock and which is independent of moderate applied
magnetic fields. The significance of remanent magnetization in
rocks is that the polarity fixation occurs during the cooling of
molten rock or the sedimentation of sedimentary rocks in response
to the magnetic field of the Earth at that particular geological
time. Thus, remanent magnetization of rocks provides a history of
Earth's magnetic field.
... ... *stratigraphically: 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.)
... ... *Quaternary: The time-frame from 1.64 million years ago
to the present.
... ... *Pleistocene: A geological epoch with the time-frame 1.64
million years ago to 10,000 years ago.
... ... *antipodal direction: In this context, "antipodes" are
diametrically opposite points on the Earth.
... ... *Miocene: The time-frame 23.3 to 5.2 million years ago.
... ... *basalt: Basalt is a dark gray to black igneous
rock of volcanic origin that cools rapidly. "Igneous rocks" are
rocks that have congealed from a molten mass.
... ... *Late Tertiary: The Tertiary is the approximate
time-frame 65 million to 1.64 million years ago.
... ... *geomagnetic dipole: In general, the best mathematical
fit to the observed geomagnetic field using a single dipole
approximation. It is usually taken as the geocentric dipole
field, which is axial and inclined at approximately 11.3 degrees
relative to the Earth's axis of rotation. The "non-dipole" field
is the difference (of the order of 5 percent) between the single-
dipole field approximation and the total planetary field.
... ... *core:  Seismic studies indicate the interior of the
Earth consists of three parts: a metallic core, a dense rocky
mantle, and a thin low-density crust. The central part of the
core is solid, but the outer part of the core is evidently
liquid. The mantle, the layer of dense rock and metal oxides
between the molten part of the core and the surface, has plastic
properties (i.e., it is a solid capable of flow under pressure). 
... ... *mantle: See previous note.
... ... *subduction: The term "subduction" refers to the
process of underthrusting of the edge of an oceanic plate (see
following notes) into the mantle underlying an adjacent plate. 
... ... *tectonic plates: See next note.
... ... *plate tectonics: The term "lithosphere" refers to the
outer layer of the Earth, comprising the crust and upper mantle,
and extending to a depth of 50 to 70 kilometers. The traditional
view of tectonics (changes in the structure of the Earth's crust)
is that the lithosphere consists of a strong brittle layer
overlying a weak ductile layer. "Plate tectonics" is the current
consensus theory that the Earth's lithosphere is broken into
fairly rigid plates, seven or eight major plates and many smaller
plates, and that convection within the underlying less rigid
"asthenosphere" causes the plates (and the associated continents
and crust) to move relative to each other. 
... ... *Cretaceous: The time-frame 145.6 to 65 million years
ago.
... ... *plagioclase feldspar: Feldspars (feldspars) are
aluminosilicates with a framework structure containing calcium,
sodium, potassium, and barium ions. This is the most abundant
mineral group in the Earth's crust. The feldspars vary in
chemical composition, and plagioclase feldspars are one type of
feldspar.
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Summary & Notes by SCIENCE-WEEK http://scienceweek.com 25May01
For more information: http://scienceweek.com/swfr.htm
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Related Background:
GEOPHYSICS: GEOMAGNETIC REVERSALS AND THE EARTH'S MANTLE
... ... G.A. Glatzmaier et al (4 authors at 3 installations, US)
now present the results of a 3-dimensional numerical computer
simulation of the geodynamo, the work designed to study the
effects of a nonuniform pattern of heat flux over the core-mantle
boundary. The authors used an improved version of a model
developed several years ago (the Glatzmaier-Roberts geodynamo
model), which produced the first dynamically self-consistent
computer simulation of the geodynamo. Essentially, the 3-
dimensional, time-dependent field equations for the
thermodynamics, velocity, and magnetic fields are solved
simultaneously as a system of differential equations, with each
field in effect constantly feeding back to the others. The
authors report the investigation of 8 different patterns of heat
flux from the core to the mantle. The authors suggest their
results indicate the existence of correlations among the
frequency of geomagnetic polarity reversals, the duration over
which the reversals occur, the magnetic-field intensity, and the
long-term geomagnetic variation {secular variation). They report
that of the examined flux patterns, the results of the case with
uniform heat flux at the core-mantle boundary appear most "Earth-
like", and that this suggests that variations in heat flux at the
core-mantle boundary of the Earth are smaller than previously
believed.
-----------
G.A. Glatzmaier et al: The role of the Earth's mantle in
controlling the frequency of geomagnetic reversals.
(Nature 28 Oct 99 401:885)
QY: Gary A. Glatzmaier: glatz@es.ucsc.edu
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Summary by SCIENCE-WEEK http://scienceweek.com 10Dec99
For more information: http://scienceweek.com/swfr.htm

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2. MATERIALS SCIENCE: MAGNESIUM DIBORIDE AS A SUPERCONDUCTOR
The recent discovery of high-temperature superconductivity in the
common compound magnesium diboride caught researchers around the
world by surprise (see related background below). Quickly enough,
however, surprise turned into a burst of activity: The discovery
was announced by preprint in January 2001; by the end of February
2001 (before the paper was published in March) 50 reports of new
research on the superconducting properties of magnesium diboride
were already posted on the Web. Considerable excitement is still
evident in the superconductor research community. (See related
background material below on superconductivity.)
... ... A.M. Campbell (University of Cambridge, UK) presents a
commentary on superconductivity in magnesium diboride, the author
making the following points:
     1) The author points out that superconductivity has
intrigued researchers since its discovery in 1911, but it took
almost 50 years for a microscopic theory based on the interaction
between electrons and the crystal lattice to explain how such a
phenomenon could exist. For real materials, the theoretical
calculations are so complex that theory cannot guide the search
for new superconductors. Phenomenological theories have
demonstrated that magnetic fields in superconductors form
quantized flux vortices that behave as Faraday lines of force,
but these theories do not predict the occurrence of new
superconductors, which are found by a combination of luck,
serendipity, and intuition.
     2) The author points out that two main classes of practical
superconductors are known: a) those that exhibit superconducting
properties below 23 kelvins, and b) those that will superconduct
at higher temperatures (30 to 164 kelvins). The present
applications of superconductors range from the most sensitive
detectors of magnetic fields ever made to the large
superconducting magnets used in body scanners and levitated
trains. The usual high-temperature superconductors are oxides
with critical temperatures above 30 kelvins. Their discovery in
1986 caused great excitement, both because of the theoretical
challenge they presented in explaining their properties and their
possible applications. Many reasonable theories have now been
proposed, and they are all consistent with most (but not all)
experimental results.
     3) The author points out that approximately 40 years ago,
hundreds of compounds were tested for superconductivity, but
magnesium diboride was missed, even though chemists had
unwittingly used this 39 kelvins superconductor to make more
complex superconductors with a critical temperature of less than
10 kelvins. It may seem surprising that magnesium diboride was
passed over given that it is a simple material readily available
from chemical suppliers. The author suggests the explanation lies
in the over 8000 possible binary compounds of the 92 elements.
-----------
A.M. Campbell: How could we miss it?
(Science 6 Apr 01 292:65)
QY: A.M. Campbell: amc1@cam.ac.uk
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Summary by SCIENCE-WEEK http://scienceweek.com 25May01
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
MATERIALS SCIENCE: A NEW HIGH-TEMPERATURE SUPERCONDUCTOR
     At temperatures close to absolute zero (-273.15 degC), the
thermal, electric, and magnetic properties of many
substances undergo dramatic changes. One such phenomenon is
superconductivity, which occurs below a critical temperature
specific for each substance that exhibits the effect.
     Superconductivity was discovered in 1911 by Heike Kamerlingh
Onnes (1853-1926), who was awarded the Nobel Prize for Physics in
1913 for his low temperature research. Kamerlingh Onnes found
that the electrical resistance of a mercury wire suddenly
disappears when the wire is cooled below a temperature of
approximately 4 kelvins. Similar behavior (but at widely
varying critical temperatures) has been found in approximately 25
other chemical elements, including lead and tin, and in thousands
of alloys and chemical compounds. Apart from these known
superconducting materials, all other substances investigated to
within fractions of a degree of absolute zero show normal (non-
superconducting) resistance to the flow of electric currents.
     For almost 50 years after the discovery of superconductivity
by Kamerlingh Onnes, there was no successful fundamental theory
that could explain the phenomenon. Finally, in 1957, an
apparently satisfactory theory of superconductivity was presented
by John Bardeen (1908-1991), Leon N. Cooper, and John R.
Schrieffer, who all shared the Nobel Prize for Physics in 1972.
The theory is now called the BCS theory of superconductivity.
     The essential aspect of BCS theory is the grouping of
electrons in superconductors in pairs ("Cooper pairs"), with the
motions of all the Cooper pairs within a single superconductor
correlated, i.e., the population of Cooper-pair electrons
constituting a system that functions essentially as a single
entity. (In quantum mechanical terms, each Cooper pair consists
of electrons of opposite spins, thus forming a spin-zero single
*boson, and the population of bosons form a *Bose-Einstein
condensate described by a single wave function.) Application of
an electric voltage to the superconductor causes all Cooper pairs
to move, the movement constituting a current. When the voltage is
removed, current continues to flow indefinitely because the
Cooper pairs (as members of a coherent condensate) are not
scattered by the atomic lattice. As a superconductor is warmed,
its Cooper pairs separate into individual electrons, and the
material becomes non-superconducting.
     Such was the theory of superconductivity for nearly 30
years, the theory successfully predicting the behavior of
superconducting materials with critical temperatures close to
absolute zero. In 1986, Karl A. Mueller and J. Georg Bednorz
discovered that certain materials exhibit superconductivity at
temperatures as high as 35 kelvins, and compounds retaining
superconductivity at temperatures as high as 160 kelvins have
since been found. Mueller and Bednorz were awarded the Nobel
Prize in Physics in 1987 for their work with high-temperature
superconductors. Such high-temperature superconductors all
contain copper and oxygen atoms that form planes or chains of
atoms in the crystal, and it is believed that anisotropy is an
important factor in their superconducting behavior. These
materials are ceramic oxides, and because they are
superconducting at temperatures easily obtainable with liquid
nitrogen, great effort has been expended to find applications for
these substances. But problems of brittleness, instabilities, and
the aggregation of impurities at surfaces have slowed progress.
Nevertheless, in contrast to superconducting ceramics,
superconducting metals and their alloys must be cooled to near
absolute zero with liquid helium, a process much more expensive
than cooling with liquid nitrogen. Superconducting ceramics thus
remain an important frontier of research in materials science.
     In terms of theory, what is significant is that BCS theory
apparently cannot provide a complete explanation of the behavior
of high-temperature ceramic superconductors. A version of BCS
theory may explain how superconductivity occurs in certain
ceramic materials, but no complete theory of high-temperature
superconductivity in ceramic materials has yet been proposed.
     Recently, researchers in superconductivity were startled
when J. Nagamatsu et al (5 authors at 2 installations, JP)
(Nature 1 Mar 01 410:63) (in a paper consisting of only 3 short
paragraphs) reported the discovery of bulk superconductivity in
the simple and readily available compound magnesium diboride
[MgB(sub2)], with magnetization and resistivity measurements
establishing a transition temperature of 39 kelvins, the
highest known critical temperature for a non-copper-oxide (non-
ceramic) bulk superconductor. [Editor's note: The surprise of
condensed-matter physicists at this new discovery is reminiscent
of the surprise of the same community at the discovery by Mueller
and Bednorz in 1986 of high-temperature ceramic superconductors.]
... ... Robert J. Cava (Princeton University, US) presents a
commentary on this new discovery, the author making the following
points:
     1) The author points out that in the ideal case of
superconductivity, the zero-resistance state is absolute:
electrons flowing in a continuous loop of superconducting wire
below the critical temperature could theoretically flow for the
age of the Universe and never lose any energy. But in the real
world there are losses, e.g., from microscopic inhomogeneities,
and the ideal is never obtained. Nevertheless, devices made with
superconducting materials have resistances orders of magnitude
lower than those of devices made with conventional conductors.
This low resistance to current means that large currents (on the
order of 10^(6) amperes per square centimeter of wire cross-
section) can be passed without significant heating. For example,
the magnets in magnetic resonance imaging instruments now in
common use are made from metal-alloy superconducting wires, and
these magnets are cooled below the critical temperature of the
metal-alloy by immersion in liquid helium at 4.2 kelvins.
     2) The author points out there are two reasons for the
current excitement concerning the discovery of superconductivity
in magnesium diboride: a) Early indications are that magnesium
diboride becomes superconducting by the BCS mechanism, so that
unlike high-temperature copper-oxide superconductors, magnesium
diboride appears to be a "conventional" superconductor. Magnesium
diboride has the highest critical temperature known for a
chemically stable, bulk compound of this type, and this suggests
the possible existence of even higher superconducting critical
temperatures in conventional and readily available materials yet
to be investigated. b) The second reason for excitement is that
it has proved so difficult to make useful wires of
superconducting ceramics. This new report by J. Nagamatsu et al
raises the possibility that superconducting materials based on
magnesium diboride may eventually be able to carry more current
than copper oxide superconductors. With a critical temperature of
39 kelvins, there is also the possibility that magnesium diboride
superconductors would not need to be cooled by liquid helium, but
could be cooled by electrical refrigerators. The author
concludes: "How much this discovery changes the path of materials
physics depends on whether magnesium diboride is a solitary
example of a new way of making high-temperature superconductors
or whether it represents only the tip of an iceberg."
-----------
Robert J. Cava: Genie in a bottle
(Nature 1 Mar 01 410:23)
QY: Robert J. Cava: rcava@princeton.edu
-----------
Text Notes:
... ... *boson: According to current physics, all particles in
nature are either fermions or bosons, with fermions (always
elementary particles) having half-integer spin (spin-states
characterized by half-integer multiples of Planck's constant
divided by 2ã), and bosons (all other particles) having integer
spin (spin-states characterized by integer multiples of Planck's
constant divided by 2ã). In general, bosons are particles that
obey *Bose-Einstein statistics, and they include photons, *pi
mesons, all nuclei having an even number of particles, and all
particles with integer or zero spin.
... ... *Bose-Einstein statistics: Bose-Einstein statistics is
the statistical mechanics of a system of indistinguishable
particles for which there is no restriction on the number of
particles that may simultaneously exist in the same quantum
energy state. Particles that obey Bose-Einstein statistics are
called "bosons".
... ... *Bose-Einstein condensate: In general, "Bose-Einstein
condensation" is a phenomenon occurring in a macroscopic system
consisting of a relatively large number of bosons at a
sufficiently low temperature (microkelvins down to nanokelvins)
in which a significant fraction of the particles occupy a single
quantum state of lowest energy (the ground state). In an atomic
Bose-Einstein condensate, several thousand atoms essentially
become a single atom, a "superatom", and this effect has been
observed experimentally with atoms of rubidium and lithium, the
atoms trapped and cooled by special methods.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 23Mar01
For more information: http://scienceweek.com/swfr.htm

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3. APPLIED MATHEMATICS: ON COMPUTING MORPHOGENESIS
Dictyostelium discoideum is an organism that has been intriguing
biologists for most of this century. Although this organism is
often called a "cellular slime mold", it is not a mold and it is
not consistently slimy. A better common name for it is a "social
amoeba". What is most remarkable about the organism is its life
cycle. In one part of its life cycle, the "organism" consists of
individual dispersed amoebas living on decaying logs, eating
bacteria and reproducing by binary fission like most other
protozoans. Then, when the local food supply becomes exhausted,  
a rather astounding event occurs: tens of thousands of these
amoebae join together to form moving streams of cells that
converge at a central point, and there they aggregate to produce
a slug (grex) 2 to 4 millimeters long. The slug migrates as a
single body towards light, and when it reaches an illuminated
area, migration ceases, and the slug differentiates into a
fruiting body composed of spore cells and a stalk, the stalk
rising approximately 1 centimeter high above the plane of the
surface on which the slug has migrated. Inside the globular end
of the fruiting body, each spore cell is cellulose encapsulated.
In the denouement, the stalk cells die and the spore cells are
widely dispersed to become new amoeba, each of which will begin a
separate new population of cells both individual and social.
Thus, in this organism, initially identical cells are
differentiated into one of two alternative cell types, spore
cells and stalk cells. It is an organism where individual cells
come together to form a cohesive structure, aggregating into a
single organism, a quite remarkable feat of organization that
challenges biologists, chemists, and physicists. Much has been
learned about this organism in the past few decades, in
particular the apparent important role of release of cyclic
adenosine monophosphate (cAMP) in the initial aggregation that
produces the slug.
... ... A.F. Maree and P. Hogeweg (University of Utrecht, NL) now
present a mathematical model of multicellular coordination in D.
discoideum, the authors making the following points:
     1) The authors point out that when individual amoebae of the
cellular slime mold D. discoideum are starving, they aggregate to
form a multicellular migrating slug, which moves toward a region
suitable for the formation of a fruiting body containing spores
(culmination). The culmination of the morphogenesis involves
complex cell movements that transform a mound of cells into a
globule of spores on a slender stalk. The movement has been
likened to a "reverse fountain", whereby prestalk cells in the
upper part form a stalk that moves downwards and anchors to the
substratum, while prespore cells in the lower part move upwards
to form the spore head. So far, however, no satisfactory
explanation for this process has been produced.
     2) The authors report they have developed a computer
simulation that demonstrates that the processes that are
essential during the earlier stages of the morphogenesis are in
fact sufficient to produce the dynamics of the culmination stage.
These processes are a) cyclic AMP (cAMP) signaling; b)
differential adhesion; c) cell differentiation; d) production of
extracellular matrix. The authors suggest their model clarifies
the processes that generate the observed cell movements. More
specifically, the authors demonstrate that periodic upward
movements, caused by chemotactic motion, are essential for
successful culmination, because the pressure waves they induce
squeeze the stalk downwards through the cell mass. The authors
suggest the mechanisms revealed by their model have a number of
self-organizing and self-correcting properties and can account
for many previously unconnected and unexplained experimental
observations.
     3) The model is a two-dimensional simulation using a hybrid
stochastic cellular automata/partial differential equation
schema. Individual cells are modeled as a group of connected
automata: the basic scale of the model is subcellular.
     4) The authors conclude: "We have demonstrated the
feasibility of such multiscale modeling for explaining the
mechanisms involved in Dictyostelium discoideum morphogenesis.
Undoubtedly, a similar approach could be adopted to unravel the
mechanisms underlying other types of developmental processes."
... ... In a commentary on the above work, Lee A. Segel (Weismann
Institute of Science, IL) states: "Can one trust simulations that
ignore much biological detail? Certainly the omission of known
phenomenology is no a priori reason to scorn a model or
simulation. For example, classical Newtonian models, bare of
relativistic or quantum effects, are universally accepted to
offer the right approach to problems ranging from bacterial
swimming to hurricane prediction. The art is to fulfill the
dictum attributed to Einstein, 'simplify as much as possible but
no further.'... [the achievement of Maree and Hogeweg] is not the
beginning of the end but rather the end of the beginning.] "
-----------
[Editor's note: The D. discoideum morphogenesis cycle is one of
the great puzzles of biology, and viewing the simulation produced
by the mathematical model of Maree and Hogeweg will no doubt
startle many biologists. Perhaps the most important consideration
is that this work provides evidence that computer modeling
involving recognized subcellular dynamic entities may soon be
used to predict (and explain) specific tissue development and
tissue morphology. The implications for both basic and medical
biology are profound.]
-----------
A.F. Maree and P. Hogeweg: How amoeboids self-organize into a
fruiting body: Multicellular coordination in Dictyostelium
discoideum.
(Proc. Natl. Acad. Sci. US 27 Mar 01 98:3879)
QY: Athanasius F.M. Maree: s.maree@bio.uu.nl
-----------
Lee A. Segal: Computing an organism.
(Proc. Natl. Acad. Sci. US 27 Mar 01 98:3639)
QY: lee@wisdom.weizmann.ac.il
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 25May01
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
CELL BIOLOGY: EFFECT OF LIGHT ON CELL MOVEMENT IN SOCIAL AMOEBAE
All biological cells possess mechanisms that effectively enable
them to sense their environment. The term "directional sensing"
refers to the ability of a cell to determine the direction and
proximity of an extracellular stimulus. Direction sensing is
needed to detect *morphogens that control *cell differentiation,
and to detect attractants that direct cell migration
(chemotaxis). The chemotaxis phenomenon is critical in immunity,
*angiogenesis, wound healing, *embryogenesis, and *neuronal
patterning. A striking example of chemotaxis is exhibited during
the life cycle of the "social" amoeba *Dictyostelium discoideum.
During growth, these cells behave as essentially individual
entities, tracking down and eating bacteria (*phagocytosis). When
the individual entities of D. discoideum are starved, they move
toward secreted *adenosine 3',5'-monophosphate (cAMP) signals,
form an aggregate (slug), and differentiate into spore and stalk
cells, with a ball of spore cells perched above the substrate on
the stalk. The fundamental role of chemotaxis in this simple and
well-characterized *eukaryote has provided a powerful system for
genetic analysis of chemotaxis, and recent observations in D.
discoideum, as well as in yeast and mammalian *leukocytes, have
clarified views of directional sensing.
... ... K. Miura and F. Siegert (University of Munich, DE) now
report a study of the effect of light on cell movement in D.
discoideum. The authors point out that in D. discoideum, although
the organism lacks specific sensory cells, the organism can
nevertheless respond in an apparently sensitive manner to
external stimuli such as temperature and light. The authors now
report that light directly modulates the cAMP cell-cell signaling
system. Light induced secretion of cAMP from the slug tips
increased the speed of cell movement. In addition, a local effect
of light on cAMP release within the slug tip could modulate cell
movement within the slug and thus control its phototactic turning
and orientation toward a light source.
-----------
K. Miura and F. Siegert: Light affects cAMP signaling and cell
movement activity in Dictyostelium discoideum.
(Proc. Natl. Acad. Sci. US 29 Feb 00 97:2111)
QY: Florian Siegert [fsiegert@zi.biologie.uni-muenchen.de]
-----------
Text Notes:
... ... *morphogens: In general, a "morphogen" is any substance
responsible for some aspect of morphogenesis (the generation of
form and structure during development of an individual organism).
... ... *cell differentiation: In general, in this context, the
term "differentiation" refers to the structural and functional
specialization of cells, developmental cell specialization
(morphology and biochemistry) resulting from activation of
specific parts of the cell genome.
... ... *angiogenesis: The origin and development of blood
vessels. Angiogenesis is an important consideration in the growth
of cancerous tumors, since the tumor provokes directed
angiogenesis into itself with the end result that the tumor is
supplied with oxygen and nutrients. Without angiogenesis, tumors
can attain only a small size before becoming self-inhibiting.
... ... *embryogenesis: In general, the formation and development
of an embryo.
... ... *neuronal patterning: The "patterning" here refers to the
patterns of connections between nerve cells, i.e., the
"circuitry".
... ... *Dictyostelium discoideum: Although often called a
"cellular slime mold", D. discoideum is not a mold, nor is it
consistently slimy. The term "social amoeba" is more accurate.
When the organism is individualized, the entities are called
"myxamoebae". When they aggregate into a slug, the organism is
called a "pseudoplasmodium" or termed the "grex". The aggregation
into a unitary grex may involve tens of thousands of individual
amoebae. (Cf. the background report that follows.)
... ... *phagocytosis: Literally, "cell eating". A cell capable
of phagocytosis (e.g., an amoeba) has a mobile boundary which can
engulf particles or smaller cells, followed by incorporation of
the particles or smaller cells into the engulfing cell interior.
... ... *adenosine 3',5'-monophosphate (cAMP; cyclic AMP): ATP
(adenosine triphosphate) is the most important chemical energy
source in all living cells, intimately involved in various cell
functions and cell metabolism, and an entity in numerous cyclic
chemical pathways involved in the synthesis of components. One of
the reaction products of ATP is cyclic AMP, which acts as an
intracellular hormone (i.e., a chemical messenger). Cyclic AMP is
derived from ATP in a reaction catalyzed by the enzyme adenylyl
cyclase (also called adenyl cyclase and adenylate cyclase).
Cyclic AMP is called the second messenger; the first messenger is
the hormone that interacts with the receptor for that hormone on
the cell surface.
... ... *eukaryote: In general, any biological cell containing
internal membrane-bound organelles such as a nucleus.
... ... *leukocytes: "White" blood cells, some types of which are
amoeba-like, exhibiting phagocytosis and pronounced chemotaxis.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 7Apr00
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
... C.A. Parent and P.N. Devreotes (Johns Hopkins University,
US) present an extensive review of recent research on cellular
directional sensing, with a focus on the signal transduction
events involved in gradient detection. The authors make the
following points:
     1) In eukaryotic cells, directional sensing is mediated by
signal pathways involving heterodimeric guanine nucleotide-
binding protein (*G protein).
     2) In D. discoideum amoebae and mammalian leukocytes, the
receptors and G protein subunits are uniformly distributed around
the cell perimeter. Chemoattractants induce the transient
appearance of binding sites for several *pleckstrin homology
domain-containing proteins on the inner surface of the cell
membrane. In gradients of attractant, these sites are
persistently present on the side of the cell facing the higher
concentration of attractant, even in the absence of a functional
*actin cytoskeleton or cell movement.
     3) Thus, the biological cell senses direction by spatially
regulating the activity of a signal transduction pathway.
-----------
[Editor's note: Although the terminology in this report is indeed
characteristic of current biology, to say that a cell "senses"
direction perhaps invites an awkward anthropomorphic connotation.
The "sensing" by biological cells in this context is no different
in character from the "sensing" by chemical reactant molecules of
each other in a non-biological solution. Certainly, the responses
of cells to chemical attractants are complicated, involving a
sequence of chemical reactions, but they are indeed chemical
reactions, and biologists consider them exactly that. In a
broader intellectual context, since all human "sensations" can
also be reduced to specific chemical reactions (or specific
chemical reactions following specific physical events), the
chemotaxis events considered here at the level of a single cell
are ultimately joined to the classical "mind vs. body"
philosophical problem.]
-----------
C.A. Parent and P.N. Devreotes: A cell's sense of direction.
(Science 30 Apr 99 284:765)
QY: Peter N. Devreotes [pnd@welchlink.welch.jhu.edu]
-----------
Text Notes:
... ... *G protein: G-proteins are a family of signal-coupling
proteins that act as intermediaries between activated cell
receptors and effectors, for example, the transduction of
hormonal signals from the cell surface to the cell interior. The
G-protein is apparently embedded in the cell membrane with parts
exposed on the outside surface and inside surface. The outside
moiety is activated by the first messenger, and the inside moiety
activates the second messenger, the G-protein thus acting as a
trans-membrane signal transducer.
... ... *pleckstrin homology domain-containing proteins:
Pleckstrin is a protein found in certain blood components, and a
"pleckstrin homology domain-containing protein" is a protein
containing a domain consisting of approximately 100 amino acid
residues found in pleckstrin and that has also been found in more
than 60 different proteins, particularly in those proteins
associated with intracellular signal transduction.
... ... *actin cytoskeleton: Actin is a family of ubiquitous
structural proteins present in all eukaryote cells, and the term
"cytoskeleton" refers to the quasi-rigid matrix that among other
things determines cell shape.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 16Jul99
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
A NEW METHOD FOR FOLLOWING INDIVIDUAL CELLS IN SLIME MOLD
... ... J.T. Bonner (who has spent more than
50 years studying the social amoeba) points out that one of the
obstacles in studying D. discoideum is that it has been difficult
to follow the movements of individual cells within the slug. The
author now describes a new method for studying D. discoideum, the
method producing flat slugs one cell thick at a mineral oil-water
interface where one can follow the movement of all the cells. The
author reports that observations of time-lapse videos reveal the
following about slug migration: 1) While the posterior cells move
straight forward, the anterior cells swirl about rapidly in a
chaotic fashion. 2) Turning of the slug involves shifting the
high point of these hyperactive cells. 3) Both the anterior and
posterior cells move forward on their own power as the slug moves
forward. 4) There are no visible regular oscillations within the
slug. 5) The number of prestalk and prespore cells is
proportionate for a range of sizes of the mini-slugs involved in
these experiments (approximately 300 to 400 cells in each of
these mini-slugs). The author suggests that all of the
observations on thin slugs are consistent with observations of
normal 3-dimensional slugs, and that experiments with 2-
dimensional slugs may provide new insights into differentiation
and movements in this organism.
-----------
J.T. Bonner (Princeton University, US): A way of following
individual cells in the migrating slugs of Dictyostelium
discoideum. (Proc. Natl. Acad. Sci. US 4 Aug 98)
QY: J.T. Bonner, Princeton University 609-258-3000
-------------------
Summary by SCIENCE-WEEK  18Sep98
For more information: http://scienceweek.com/swfr.htm

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

4. CELL BIOLOGY: ION CHANNEL PROTEINS AND CALCIUM CHANNELS
     The regulated permeabilities of the biological cell membrane
to various ions are important factors in a number of crucial
cellular mechanisms. In general, these permeabilities involve
specific ion-selective pores constructed of proteins, the pores
called "ion channels", with ion channels of different types
available for any one ion species. Evidence suggests that an ion
channel protein spans the membrane and has a central water-filled
pore open to both the intracellular and extracellular
compartments. On each side, the pore widens to form a vestibule,
with the restricted region within the plane of the membrane
containing an effective "gate" that can open or close to control
the passage of ions.
     Ion channels are highly regulated, linked to key cellular
processes, and during the past two decades, an intensive effort
in many laboratories has led to identification of the proteins of
some ion channels, studies of the configuration of these
proteins, and an improved understanding of the complex events
associated with the passage of simple ions such as sodium,
potassium, calcium, and chloride into and out of biological
cells. A very powerful technique used in much of this work
involves genetic engineering of ion channels. The essential idea
is to isolate a DNA sequence that encodes the protein for a
particular ion channel, then transfect this DNA sequence into the
genome of a host cell type amenable to detailed electrical and
transport measurements. When the ion channel protein is expressed
in this host cell and becomes part of the host cell plasma
membrane, the various properties of the ion channel become open
to investigation. Although the results of such experiments must
be carefully interpreted, the ability to make specific and
discrete alterations in channel protein membrane structure has
led to important insights into the relation between the
structures of ion channel proteins and their control of ion
permeabilities.
     Of the ions that diffuse back and forth across cell
membranes, calcium ions are of great importance in many
physiological processes. In biological cells, extracellular and
intracellular concentrations of calcium ion differ by several
orders of magnitude, and cells are therefore exposed to a steep
calcium ion gradient across their membranes. In general, the
control of cellular calcium ion is maintained by an elaborate
system of channels, exchangers, and pumps located both in the
plasma membrane and in intracellular membranes.
... ... James W. Putney Jr. (National Institutes of Health, US)
presents a commentary on recent studies of a calcium ion channel
(L. Yue et al: Nature 2001 410:705), with the author (Putney)
making the following points:
     1) The author points out that calcium ions are important
biological signals, controlling processes such as protein
secretion, muscle contraction, cell death, and tissue
development. In general, calcium signalling involves an increase
in the intracellular concentration of calcium ions, and one of
the mechanisms by which this occurs is so-called "capacitative
calcium entry" (also called "store-operated calcium entry"), a
process that requires the regulated opening of ion channels in
the plasma membrane. These ion channels, however, have not yet
been identified. (The process is called "store-operated calcium
entry because it is somehow activated by a fall in the
concentration of calcium ions stored in an internal membrane
system, the endoplasmic reticulum.)
     2) Yue et al now present evidence that implicates a newly
discovered protein (CaT1) as a constituent of a capacitative
calcium-entry channel, and the author (Putney) suggests this
discovery may lead to an improved understanding of the cellular
and molecular mechanism by which this channel is controlled.
     3) The author (Putney) points out that although the weight
of evidence supports the conclusion of Yue et al that the protein
CaT1 (or, in some instances, a closely related protein [ECaC])
constitutes the ion-conducting pore of the calcium channel they
investigated, there are also other calcium-specific channels,
known from electrophysiological studies, that have properties
distinct from the channel investigated by Yue et al. Putney
points out that it is possible and even likely that other channel
proteins form part of these channels. Putney concludes: "In the
near future, I anticipate continuing progress in the search for
the complete molecular definition of the capacitative calcium-
entry channels, as well as a solution to the mystery of how they
are regulated."
-----------
James W. Putney Jr.: Channeling calcium.
(Nature 5 Apr 01 410:648)
QY: James W. Putney Jr.: putney@niehs.nih.gov
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 25May01
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
NEUROBIOLOGY: INTRACELLULAR CALCIUM IONS AND NERVE GROWTH CONES
After neurons have differentiated and migrated to their intended
specific destinations, they extend *axons that select connection
targets from an enormous number of possibilities, and eventually
these axons form *synapses with appropriate cells in the target
region. These events depend on a complex of cellular and
molecular signals that guide axons and facilitate correct
connections. The signals involve *cell adhesion molecules that
regulate the interactions between axons and the surfaces upon
which they grow, diffusible molecules that attract growing axons,
and a family of molecules called "*neurotrophins" that promotes
and maintains stable synapses between axons and their targets.
The circuitry of the developing nervous system is thus gradually
constructed by means of such intricate interactions. The local
dynamics of growing axons are now known to involve the properties
of the "growth cone", a specialized structure at the tip of the
extending axon. Growth cones are highly motile structures that
explore the extracellular environment and respond to local cues
by changing the speed or direction of growth. Experiments
indicate that in vitro the intracellular calcium ion
concentration of growth cones is correlated with their motility,
but the links between environmental cues and axon growth in vivo
are unknown.
... ... James Q. Zheng (Univ. of Medicine and Dentistry of New
Jersey, US) now reports new evidence concerning the role of
calcium ion in nerve growth cone directionality, the author
making the following points:
     1) Although guidance of developing axons involves turning of
the growth cone in response to a variety of extracellular cues,
little is known concerning the intracellular mechanism by which
the directional signal is transduced. Calcium ion is apparently a
key "*second messenger" in growth cone extension and has been
implicated in growth-cone turning.
     2) The author reports that with cultured amphibian neurons
(Xenopus laevis; African clawed toad) a direct spatially
restricted elevation of intracellular calcium ion concentration
on one side of the growth cone by focal laser-induced photolysis
(FLIP) of caged calcium ions consistently induced turning of the
growth cone to the side with elevated calcium ion concentration.
Furthermore, when the resting intracellular calcium ion
concentration at the growth cone was decreased by the removal of
extracellular calcium ion concentration, the same focal elevation
of intracellular calcium ion concentration by FLIP induced
repulsion.
     3) The authors suggests these results provide direct
evidence that a localized calcium ion signal in the growth cone
can constitute the intracellular directional cue for extension,
and this cue is sufficient to initiate either attraction or
repulsion, depending on ambient conditions. By integrating local
and global calcium ion signals, a growth cone could thus generate
different turning responses under different environmental
conditions during guidance. The author concludes: "Such diversity
of regulation along the signal transduction pathway... could
provide the potential for the specific and accurate wiring of
millions of axons through a limited number of cues available
during development."
-----------
James Q. Zheng: Turning of nerve growth cones induced by
localized increases in intracellular ions.
(Nature 6 Jan 00 403:89)
QY: James Q. Zheng [zhengiq@umdnj.edu]
-----------
Text Notes:
... ... *axons: In those animals that have nervous systems, one
task of embryological development is to ensure the proper
functional connections between nerve cells and other nerve cells,
and between nerve cells and muscle cells. The innervation must be
exact, in the sense that the growing nerve cell extension (the
axon), which will ultimately serve to propagate information, must
reach a specific and often distant target. In humans, for
example, there are nerve cells whose growing axons reach specific
targets as much as a meter distant from the cell body.
... ... *synapses: The junction between the terminal of the axon
of one neuron and another neuron is called a "synapse".
 ... ... *cell adhesion molecules: In general, substances that
regulate the interactions between axons and the surfaces upon
which they grow.
... ... *neurotrophins: In general, neurons in the central
nervous system apparently depend for their survival on a number
of secreted substances called neurotrophins (neurotrophic
factors). These substances are polypeptides of 200 to 300 amino
acids, and at least 4 different neurotrophins have been
identified.
... ... *second messenger: In general, the "second messenger" is
an intermediary compound that couples extracellular signals to
intracellular processes with amplification of the transduced
signal.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 28Apr00
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
NEUROBIOLOGY: MODIFICATION OF DENDRITIC SPINES BY CALCIUM
     Nerve cells (neurons), the cellular units of all nervous
systems, have diverse morphologies within an individual, and a
variety of unique morphologies across species. In general,
however, all neurons have two fundamental anatomic components: a
cell body (soma) and a single long filamentary extension from the
cell body, the so-called "axon" (which may branch along its
length), that propagates electrical activity from the cell body
(or from the vicinity of the cell body) to other locations (e.g.,
to muscle cells or to other nerve cells).
     Most neurons also possess a third anatomic component:
extensions of the cell body (few or numerous) that provide
junction points for the axons of other neurons (i.e., provide
surface area for synapses), and thus serve as loci for receiving
inputs. In some neurons, dendrites are extensively branched
(arborized), the single neuron as a whole receiving inputs from
as many as 100,000 other neurons, while at the other extreme
there are neurons with only one dendrite receiving input from
only one or a few other neurons.
     During the past several decades, the detailed anatomy of
dendrites has been a focus of much research, in particular the
often-present parts of dendrites called "dendritic spines". These
spines are small (1 to 2 microns) thorn-like protuberances along
the length of a dendrite, and there is evidence that such spines
may be important components in many kinds of neural
microcircuits. In the human nervous system, dendritic spines are
especially prominent in the *cerebellar cortex, *basal ganglia,
and *cerebral cortex, and in the cerebral cortex approximately 80
percent of all *excitatory synapses are evidently made onto
dendritic spines, whereas only approximately 30 percent of
*inhibitory synapses are made onto dendritic spines. Currently,
neurobiologists have ascribed literally dozens of different
functions to dendritic spines, and investigations of these
structures are underway in many laboratories.
... ... Kristen M. Harris (Boston University, US) presents a
commentary on current research concerning the involvement of
calcium ions in dendritic spine morphology, the author making the
following points:
     1) Since the discovery of dendritic spines at the turn of
the century by *Ramon y Cajal (1852-1934), these structures have
been of interest to neurobiologists because of their special
morphology and their possible involvement in cognitive functions
such as learning and memory.
     2) Dendritic spines have diverse shapes that range more than
100-fold in size. Larger spines have proportionately larger
synapses and more diversity in subcellular organelles and
molecular composition, and such differences may be involved in
functional differences of the synapses located upon spines.
     3) Existing data suggest that spines are maintained by
optimal activation: more spines form when neurons have less
excitatory activation, and spines are lost when activation is too
high or when presynaptic axons degenerate. This pattern suggests
that neurons may *homeostatically regulate input by means of the
number of axon-dendritic spine synapses.
     4) New evidence by Korkotian and Segal (1999) now points to
the release of calcium ions from intracellular stores as a
possible modulator of dendritic spine structure. When neurons in
culture are exposed to caffeine, calcium is released from the
intracellular stores into dendrites and dendritic spines, and
under these conditions most of the dendritic spines elongate
approximately 33 per cent during the following several hours.
     5) The finding that release of calcium from intracellular
stores might have a direct effect on dendritic spine structure is
especially interesting because changes in spine structure have
long been thought to be an important mechanism of memory. The
increase in intraspine calcium caused by release of calcium from
intracellular stores is much less than the increase in intraspine
calcium resulting from high synaptic activity (which decreases
the number of spines), and this suggests that a small increase in
intraspine calcium causes a spine to elongate, whereas high
intraspine calcium from excessive activity causes a spine to
collapse. Thus, spine morphology may be closely regulated by
local intracellular calcium ion concentration.
-----------
Kristen M. Harris: Calcium from internal stores modifies
dendritic spine shape.
(Proc. Natl. Acad. Sci. US 26 Oct 99 96: 12213)
QY: Kristen M. Harris [kmharris@bio.bu.edu]
-----------
Text Notes:
... ... *cerebellar cortex: The cerebellum is a large neural
structure at the base of the brain involved in motor
coordination, posture, and balance. The cortex of the cerebellum
is a thin corrugated outer layer containing cell bodies of
cerebellar neurons.
... ... *basal ganglia: The term "basal ganglia" refers to a
group of nuclei lying deep in the subcortical white matter of the
frontal lobes, these nuclei involved in the organization of motor
behavior. In this context, a "nucleus" is a cluster of nerve
cells.
... ... *cerebral cortex: The cerebral cortex is a thin surface
layering of nerve cells of the brain, the region only  several
millimeters thick but covering all of the brain surface. This is
the part of the central nervous system most intimately involved
with the so-called "higher faculties", although the cortex
operates in concert with other parts of the brain. The structure
is primitive in lower mammals, and is found progressively more
pronounced and with greater surface area in primates and man.
... ... *excitatory synapses: A synapse which when activated
produces excitation of the postsynaptic nerve cell.
... ... *inhibitory synapses: A synapse which when activated
produces inhibition of the postsynaptic nerve cell.
... ... *Ramon y Cajal (1852-1934): Santiago Ramon y Cajal is one
of the more important historical figures in neurobiology. His
specialty was the histology of the nervous system as revealed by
cellular staining. By 1889 he worked out the connections of the
cells of the gray matter of the brain and spinal cord with a
demonstration of the extreme complexity of the system. He also
worked out the structure of the retina of the eye. He established
the "neuron theory", which postulated the nervous system to
consist entirely of individual nerve cells and their processes.
In 1906, Ramon y Cajal shared the Nobel Prize in Physiology and
Medicine with Camillo Golgi (1843-1926), whose stains for the
nervous system were used by Ramon y Cajal in his work.
... ... *homeostatically regulate: The term "homeostasis" refers
to a physiological equilibrium necessary in general for the
viability of an organism, and in particular for the operation of
many cellular functions. Homeostatic mechanisms in biological
systems usually involve an element of negative feedback
signaling. In vertebrates, for example, when blood temperature is
too high, temperature receptors provoke a sequence of events
involving many pathways that ultimately results in a lowering of
body temperature. Similar homeostatic mechanisms operate at
cellular levels. 
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 24Dec99
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
MOLECULAR CHARACTERIZATION OF A NEURONAL CALCIUM CHANNEL
Ion channels are protein channels in cell membranes that allow
ions to pass from extracellular solution to intracellular
solution and vice versa. Most ion channels are selective,
allowing only certain ions to pass, and an individual cell has
ion channels with various ion selectivities. The selectivity of
an ion channel can be "gated", the channel effectively opened or
closed, and ion channels are said to voltage-gated or ligand-
gated, depending on how the change in selectivity is provoked.
The term "T-type channels" refers to channels whose ion currents
are both transient (due to rapid inactivation) and small (due to
small conductance), and such ion channels are believed to be
involved in pacemaker activity, low-threshold calcium ion spikes,
neuronal oscillations, etc. Frog oocytes are frog egg cells, and
they are a common laboratory vehicle for expressing the proteins
of genetically engineered material from other species and
coupling this expression with electrophysiological measurements
of frog oocyte membrane behavior. ... ... Perez-Reyes et al (9
authors at 4 installations, US UK) report the identification via
cloning methods of a neuronal T-type calcium ion channel, with
expression of the protein constituting the channel in frog
oocytes, and electrophysiological characterization of the channel
in these cells. The authors suggest they have cloned the first
member of the low-voltage-activated T-type Ca(sup2+) family, and
one with identified human and mouse genetic homologues.
QY: Edward Perez-Reyes: eperez@luc.edu
(Nature 26 Feb 98) (ScienceWeek 13 Mar 98)
For more information: http://scienceweek.com/swfr.htm

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

5. BIOCHEMISTRY: ON PROTEIN FOLDS AS NATURAL FORMS
     Proteins are polymers consisting of long chains of amino
acid residues, but that is only the beginning of their functional
chemistry. In biological systems, proteins assume various complex
high-order configurations ("folding"), and it is these
configurations that usually determine the roles of proteins as
biochemical entities in the biological system. An important goal
of molecular biology is to understand the structural and
functional features of proteins, in particular the mechanisms
responsible for specific protein folding.
     The term "alpha helix" refers to a spiral configuration of a
polypeptide chain in which successive turns of the helix are held
together by hydrogen bonds between the amide (peptide) links, the
carbonyl group of any given residue being hydrogen-bonded to the
imino group of the 3rd residue behind it in the chain. The term
"beta sheet" (beta-pleated sheet) refers to an array of two or
more "beta strands", with each beta strand consisting of two
polypeptide chains in a so-called "beta configuration", which in
turn is a stable configuration of a polypeptide chain in which
the chain is almost fully extended and hydrogen-bonded to an
adjacent polypeptide chain.
     In this context, the term "natural forms" refers to forms
that are an apparent intrinsic part of the natural order of the
world, for example, inorganic forms such as atoms or crystals.
... ... M. Denton and C. Marshall (University of Otago, NZ)
present an essay on protein folds as natural forms, the authors
making the following points:
     1) The authors point out that a protein fold consists of a
folded chain of between 80 and 200 amino acids, with some
proteins possessing a single fold, but most proteins having a
combination of two or more folds. During the 1970s, as the 3-
dimensional structure of an increasing number of folds was
determined, it became apparent that the folds could be classified
into a finite number of distinct structural families containing a
number of closely related forms. The fact that protein folds
could be classified in this manner provided the first line of
evidence that the folds might be natural forms.
     2) The authors point out that further evidence that protein
folds do indeed represent a finite set of natural forms is
provided by detailed structural studies during the past two
decades, these studies revealing that the structure of protein
folds can be accounted for by a set of "constructional rules"
that govern the manner in which the various secondary structural
motifs, such a alpha-helices and beta-sheets, can be combined and
packed into compact 3-dimensional structures.
     3) The authors suggest that considerations of these
"constructional laws" indicates that the total number of
permissible protein folds is bound to be restricted to a very
small number -- approximately 4000, according to one estimate.
Other estimates suggest the total number of protein folds used by
living organisms may not be more than 1000. The authors state:
"Whatever the final figure, the fact that the total number of
folds represents a tiny stable fraction of all possible
polypeptide conformations, determined by the laws of physics,
reinforces the notion that the folds, like atoms, represent a
finite set of built-in natural forms."
-----------
M. Denton and C. Marshall: Laws of form revisited.
(Nature 22 Mar 01 410:417)
QY: Michael Denton: Dept. of Biochemistry, University of Otago,
PO Box 56, Dunedin 9001, NZ.
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 25May01
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
MOLECULAR BIOLOGY: NATURAL HISTORY AND PROTEIN FOLDING
Although the term "evolution" is usually applied to the natural
history of entire organisms, another perspective is to consider
the evolution of biological molecules, particularly the protein
biomolecules. The proteins of an organism, the end products of
the working of genes, evolve just as genes evolve, and an
important question is how knowledge of the evolution of proteins
can be used to understand protein dynamics.
... ... Steven A. Benner (University of Florida, US) presents an
essay on the natural history of biomolecules, the author making
the following points concerning natural history and protein
folding:
     1) The author suggests that many chemical biologists and
biophysicists view the future of biology as a metamorphosis in
which understanding of biological phenomena will be replaced by
understanding of the interactions of their underlying
physicochemical components. This metamorphosis is already ongoing
and very productive, but it is unlikely to be the entire story.
The author suggests the surprise will come when biophysicists and
chemical biologists discover that they need to research the
history of biomolecules if they are to understand the physical
behaviors they are attempting to characterize.
     2) One example of the need for natural history is the
problem of protein folding. Physical chemists have mounted a
frontal assault on this problem, using computers to build
physical models of proteins in water, the models involving
guesses concerning many aspects of atomic interactions. The
assault has failed. The only way to make such a computation even
vaguely tractable requires considerable abstraction of the
physical model for the protein, and the same physical theory that
inspired the computation indicates that these abstractions must
compromise the value of the computation as a predictive tool.
     3) Natural history offers an entirely different approach to
protein folding. Divergent evolution creates families of proteins
that have descended from common ancestors. As proteins evolve
from these ancestors, natural selection requires them to remain
"fit". The principal prerequisite for fitness in a protein is a
particular folding of the protein, so proteins that diverge from
a common ancestor generally conserve their folds. This means that
during the evolution of protein sequences, mutations do not
accumulate as they would if proteins were formless and
functionless organic molecules. Instead, amino acids that are
important to the fold experience substitution differently from
those amino acids that are not important to the fold. A signal
should lie in the pattern of protein-sequence divergence -- the
difference between how proteins have divergently evolved in the
past, and they would have evolved had they been formless and
functionless molecules.
     4) At present, the *secondary and tertiary structure of
proteins can reliably be predicted by exploiting the historical
signal embedded in a set of protein sequences related by common
ancestry. Since 1990, approximately 30 protein folds have been
predicted using the history of protein families. In many cases,
the prediction provided information about the function as well as
about the form of the protein.
-----------
Steven A. Benner: Natural progression.
(Nature 25 Jan 01 409:459)
QY: Steven A. Benner: Dept. of Chemistry, Univ. of Florida, PO
Box 117200, Gainesville, FL 32611 (US).
-----------
Text Notes:
... ... *secondary and tertiary structure: In general, the
structures of biopolymers are denoted as follows: 1) Primary
structure: The sequence of subunits that comprise the
macromolecule (e.g., the amino acid sequence of a protein). 2)
Secondary structure: The localized arrangement in space of
regions of a biopolymer (e.g., the alpha-helix). 3) Tertiary
structure: The 3-dimensional configuration of a biopolymer. 4)
Quaternary structure: The 3-dimensional arrangement and
constitution of a multimeric macromolecule (i.e., a substance
containing more than one biopolymer; an entity consisting of
biopolymer subunits. (Also, see related background material
below.)
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 9Feb01
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
BIOCHEMISTRY: PHYSICAL BASIS FOR PROTEIN SECONDARY STRUCTURE
     The term "protein" was first used by the chemist Gerardus
Mulder (1802-1880) to denote the basic building block of the heat
coagulable (albuminous) material found in living systems, but it
was not until the 1920s that proteins were generally recognized
as a special type of macromolecule (a polypeptide) and studied as
polymers. Currently, biochemists and protein chemists distinguish
four orders of polymeric structure in proteins:
     1) The term "primary" structure refers to the linear
structure of the polypeptide as determined solely by the number,
sequence, and type of amino acid residues.
     2) The "secondary structure" of a protein is determined by
interactions between the sequential units, particularly hydrogen
bonding between particular amino acids and nonpolar interactions
between hydrophobic regions, the interactions producing, in
general, three local or global secondary structure variants:
alpha helix, beta sheet, and tight turn. An "alpha helix" is a
spiral configuration of a polypeptide chain in which successive
turns of the helix are held together by hydrogen bonds between
the amide (peptide) links, the carbonyl group of any given
residue being hydrogen-bonded to the imino group of the 3rd
residue behind it in the chain. The term "beta sheet" (beta-
pleated sheet) refers to an array of two or more "beta strands",
with each beta strand consisting of two polypeptide chains in a
so-called "beta configuration", which in turn is a stable
configuration of a polypeptide chain in which the chain is almost
fully extended and hydrogen-bonded to an adjacent polypeptide
chain. The third secondary structure variant, "tight turn" (beta
bend; beta turn) refers to a bending of a short stretch of
polypeptide chain that allows the main direction of the chain to
change. The turn consists of 4 amino acid residues in which the
CO group of residue n is hydrogen-bonded to the NH group of
residue n + 3.
     3) The "tertiary structure" of a polypeptide is a 3-
dimensional configuration, a folding or coiling of the molecule
primarily determined by interactions of hydrophobic regions and
to a lesser extent by hydrogen bonding.
     4) The "quaternary structure" of proteins is characterized
by the interaction of 2 or more individual polypeptides, often
via disulfide bonds, the result a larger functional molecule.
     Although given the above rough categorization of protein
structures, there are many aspects that might be of interest,
there are two salient generalizations concerning proteins which
command attention: a) when, as the result of the expression of a
gene, a specific protein is synthesized in a living system, that
protein rapidly assumes a configuration specific for its type;
and b) whatever it is that a specific protein does in a living
system, that action is dependent primarily and directly on its
configuration rather than on its specific amino acid sequence.
These two generalizations form the basis for much of the research
on protein structure, with two resultant questions: a) What rules
govern the rapid folding into a particular configuration by a
protein? and b) How is the particular configuration of a protein
related to its biochemical actions in the living system? The
first question is currently viewed as a problem in the physical
chemistry of macromolecules, and research on the question has
been heavily theoretical, with models based on a wide range of
quantitative techniques.
     The problem of protein folding is essentially as follows:
Given an ordinary polypeptide, the number of possible
configurations is astronomical. If a particular protein always
assumes the same configuration in a living system (its "native
configuration"), and if that configuration represents some sort
of energy minimum for the polypeptide chain, how does the protein
find that energy minimum within milliseconds? Does the protein
pass through every possible configuration state until the energy-
minimum configuration is "discovered"? Or are there constraints
that reduce the number of possible configurations to a much
smaller number? As easy as it is to state this problem, the
problem is a puzzle that has confounded researchers for 40 years.
... ... R. Srinivasan and G. Rose (Johns Hopkins University, US)
present a physical theory for protein secondary structure, the
authors making the following points:
     1) The authors propose a physical theory for secondary
protein structure based on steric and local interactions, and
suggest their finding demonstrate that local, intrinsic,
sequence-dependent biases toward helix, strand, and turn
configurations are densely dispersed throughout the polypeptide
chain and are unlikely to be merely accidental. The authors
report tests of the theory by *Monte Carlo simulations.
     2) The authors suggest that in essence, secondary structure
bias is largely a consequence of the balance between two opposing
local forces that govern the position of equilibrium between the
two mainchain states of contraction or extension. The competing
forces are attractive local interactions vs. sidechain
conformational restriction.
     3) The authors point out that C.B. Anfinsen (1973) proposed
that proteins attain their native state by folding to a global
minimum of *Gibbs free energy, and that this hypothesis has
usually been interpreted to mean that the native conformation of
individual molecules also corresponds to a global minimum in
internal energy because a fully folded protein will have lost its
*conformational entropy, or almost so. Thus, conformational
entropy is thought to play an insignificant role in the
thermodynamics of protein folding. Specifically, the statistical-
mechanical- (Boltzmann-) weighted populations of any two states
are thought to depend predominantly on their energy difference.
In contrast, the work of the authors suggests the conclusion that
conformational entropy is the main factor that discriminates
between two energetically equivalent (degenerate) ground states,
and in so doing "preorganizes" the protein.
     3) The authors point out that the problem of secondary
structure is intimately related to the Levinthal paradox [C.
Levinthal (1969)], which argues that a folding protein does not
"explore" conformational hyperspace freely; otherwise, the
protein would encounter an insoluble search problem. For
Levinthal, this insight was not a paradox at all, but a
convincing demonstration that some intrinsic constraint limits
the effective size of the conformational space. In this view,
proteins solve the "multiple-minimum problem" not by an extensive
search that identifies the deepest minimum, but by a limited
search that avoids false minima. The existence of intrinsic bias
resolves this paradox by prejudicing the ensemble of available
folding trajectories toward the native minimum. Thus, a folding
protein need not discriminate among an astronomical number of
conformations, because intrinsic bias "steers" the molecule
toward a high degree of preorganization. [*Note #1]
     4) In summary, the authors suggest their analysis has
demonstrated that pronounced biases toward protein secondary
structure are present in natural protein sequences, that these
biases have a discernible physical basis, and that their
existence suggests reinterpretations of current folding models.
-----------
R. Srinivasan and G. Rose: A physical basis for protein secondary
structure.
(Proc. Natl. Acad. Sci. US 7 Dec 99 96:14258)
QY: George D. Rose: rose@grserv.med.jhmi.edu
-----------
Text Notes:
... ... *Monte Carlo simulations: In general, a "Monte Carlo
method" is any method for obtaining a statistical estimate of a
desired quantity by random sampling. In the most successful
applications, the desired quantity is a statistical parameter,
and the sampling is made from an artificial population that may
be a model of the physical system itself. The method is of
considerable utility in handling certain intractable applied
mathematical problems.
... ... *Gibbs free energy: (Gibbs function; thermodynamic
potential) A thermodynamic function of a system. In the present
context, if a system is considered at constant pressure and
temperature, and the only work done is that caused by changes in
volume, it can be shown that the system is in equilibrium when
the Gibbs free energy has a minimum value.
... ... *conformational entropy: In general, the entropy of a
system is a measure of the unavailability of its internal energy
to do work in a cyclic process. From the standpoint of
statistical mechanics, entropy is in general a measure of the
disorder of a system. The term "conformational entropy" refers to
that part of the total entropy of a system due to specific
orientations of atoms.
... ... *Note #1: In this paragraph, terms such as "hyperspace"
and "trajectory" derive from statistical mechanics and the
following considerations: If the state of a system depends upon N
variables, the state of the system can be viewed as a point
(phase point) in an N-dimensional space (phase space; system
hyperspace), and as the state of the system changes, its phase
point can be viewed as describing a trajectory in its phase
space. There are certain systems for which qualitative analysis
of the phase space trajectories of the system reveals significant
properties of the system otherwise difficult to delineate.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 28Jan00
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
ON EXPLANATIONS OF PROTEIN FOLDING
Since the 3-dimensional configuration of a protein is an
essential determinant of what the protein does in a biological
system, protein "folding", the process that leads to this
configuration, is a central focus in biophysical chemistry.
... ... William A. Eaton (National Institutes of Health, US)
presents a review of current research in this field, the author
making the following points:
     1) There are two aspects to the problem of protein folding.
The first is predicting the 3-dimensional structure of a protein
from its amino acid sequence; the second is to understand _how_
proteins fold. The problem of protein folding has recently
assumed additional importance as more and more human diseases
(e.g., Alzheimer's and Parkinson's diseases) are believed to be
caused by aggregation of misfolded proteins.
     2) The question of _how_ a protein folds can be phrased more
precisely as follows: What are the sequences of structural
changes that occur in a polypeptide as it finds its way from the
myriad of possible structures in the *denatured state to the
final unique *native structure? How many different folding routes
exist, and what are their relative probabilities?
     3) Until approximately a decade ago, the problem of
understanding how proteins fold was addressed by identifying and
characterizing one or two metastable structures believed to be
obligatory intermediates in a sequential process along a well-
defined protein-folding pathway. The prevailing view was that
structural characterization of such intermediates would give the
clue to the basic underlying mechanism, as in the study of
organic chemical reactions. However, unlike small-molecule
chemical reactions, in which covalent bonds are broken and new
bonds formed in a structurally well-defined transition state, the
many degrees of freedom of a polypeptide chain demand a different
approach. A polypeptide of 100 amino acids has a huge number of
conformations, even if only a tiny fraction of the more than
2^(100) (= 10^(30)) possible conformations are thermally
occupied. Understanding the complexities of protein folding at
the microscopic level, and developing models that make
quantitative predictions, therefore requires a statistical
approach, i.e., the theoretical and computational tools of modern
statistical mechanics.
     4) Nonexponential kinetics have played an important role in
understanding conformational changes in native proteins. They are
particularly interesting for protein folding because they could
arise from a process that is "downhill" in free energy, i.e, one
in which the overall free energy barrier separating the native
from the denatured state is very small or nonexistent. For large
barriers, only the structures of the initial and final states are
observable, because structures along the folding route are too
sparsely populated. If, however, the barrier becomes very small
or disappears altogether, all of the structures can in principle
be detected and characterized by spectroscopy.
     5) At the present time, there exists the exciting prospect
of performing single molecule experiments for direct exploration
of the energy landscape and folding routes. Finding proteins that
fold with a "downhill scenario" is an essential first step in
this quest. That some proteins will exhibit downhill folding,
moreover, is one of the novel theoretical predictions of an
energy landscape analysis of protein folding.
-----------
Editor's note: In addition to the background material below, see
the 8 Aug 99 issue of SW (#32), report #3)
-----------
William A. Eaton: Searching for "downhill scenarios" in protein
folding.
(Proc. Natl. Acad. Sci. US 25 May 99 96:5897)
QY: William A. Eaton [eaton@helix.nih.gov]
-----------
Text Notes:
... ... *denatured state: In biochemistry, the term
"denaturation" refers to the complete unfolding
and loss of catalytic activity of a protein.
... ... *native structure: The "native" structure or
configuration of a biological macromolecule is the functional
state or configuration ordinarily assumed by the molecule in the
biological system in which the molecule occurs.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 3Sep99
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
PROTEIN FOLDING: ON OLEG PTITSYN (1929-1999)
... In recent decades, one of the leading personalities in the
field of protein folding was Oleg Ptitsyn (1929-1999). For nearly
30 years, Ptitsyn advocated the concept of the "molten globule"
as a key intermediate in protein folding. Ptitsyn's fundamental
idea that proteins can adopt compact structures without the
close-packed side-chain interactions characteristic of *native
proteins is now implicit in virtually every discussion of the
subject.
... ... C.M. Dobson and R.J. Ellis (2 installations, UK) present
a biographical essay on Oleg Ptitsyn, the authors making the
following points:
     1) Ptitsyn was born in Leningrad in 1929, and he received a
doctorate in physics from the University of Leningrad at the age
of 25. His early work was on the physics of polymers at the
Institute of High Molecular Weight Compounds in Leningrad, but he
soon became interested in proteins and began work on protein
folding. With others, Ptitsyn founded the Institute of Protein
Research in Pushchino, a town approximately 70 miles from Moscow.
     2) In the early 1970s, Ptitsyn speculated that the protein-
folding problem might be made much simpler if a polypeptide chain
folds first into a flexible state with the usual positioning of
*helices and sheets, but without the intricate and detailed
packing of the various side chains found in a fully native
protein. There was no experimental evidence for this proposal at
that time, but soon such evidence began to emerge from studies of
*protein denaturation in various laboratories.
     3) Ptitsyn introduced the strategy of a combination of
physical methods to search for this new state of proteins. The
name "molten globule" was first used by Akiyoshi Wada in Japan.
The Ptitsyn laboratory subsequently made the major advance of
identifying species in kinetic experiments that fitted Ptitsyn's
definition of a molten globule, and then relating this state to
the mechanism of the folding process itself.
     4) Concerning Ptitsyn the person, the authors write: "Oleg
Ptitsyn was a gentle, kindly person, whose diminutive and
bustling figure was familiar around the conference and lecture
halls of the world... He died on 22 March, just before he was due
to give a lecture at the University of Warwick, during one of his
frequent trips to Britain. It was as he would have wished. He
died, as he had lived, earnestly engaged in the practice of
science, and looking forward to intense discussions about his
latest ideas."
-----------
C.M. Dobson and R.J. Ellis: Oleg Ptitsyn (1929-1999).
(Nature 8 Jul 99 400:122)
QY: Christopher M. Dobson [chris.dobson@chem.ox.ac.uk]
-----------
Text Notes:
... ... *native proteins: The "native" state or configuration of
a biological macromolecule is the functional state or
configuration ordinarily assumed by the molecule in the
biological system in which the molecule occurs.
... ... *helices and sheets: The "primary structure" of a
polypeptide chain is the actual sequence of amino acid residues;
the "secondary structure" is a low-order folding of the chain;
the "tertiary structure" is a high-order folding of the molecule.
Concerning the secondary structure, there are two main types: the
alpha configuration is a spiral configuration in which successive
turns of the helix are held together by hydrogen bonds; the beta
configuration is a configuration in which the chain is almost
fully extended and hydrogen bonded to an adjacent polypeptide
chain, with successive chains often involved to form "sheets".
... ... *protein denaturation: Usually irreversible complete
protein unfolding (without rupture of peptide bonds) and loss of
catalytic activity if the protein is an enzyme.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 6Aug99
For more information: http://scienceweek.com/swfr.htm

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6. HISTORY OF BIOLOGY: ON THE DISCOVERY OF HEMATOBLASTS
     Whole blood, perhaps the most important tissue of the human
body after the brain, comprises 8 percent of total body weight.
By weight of blood, 55 percent is "plasma", a watery liquid
containing dissolved substances (mostly proteins), and 45 percent
consists of so-called "formed elements" -- cells and cell
fragments. These cells consist of 3 types: red blood cells
(oxygen-transporters; erythrocytes), white blood cells (immune
system cells; leukocytes) and "platelets" (cell fragments
involved in blood clotting; thrombocytes). Densities of these
cells per cubic millimeter of blood are: erythrocytes 4.8 to 5.4
million; leukocytes 5000 to 10,000; thrombocytes 250,000 to
400,000.
     The process by which the cells of the blood are formed is
called "hemopoiesis" (hematopoiesis). During embryonic and fetal
life there are several centers for blood cell production: the
yolk sac, liver, spleen, thymus gland, lymph nodes, and bone
marrow. After birth, however, hematopoiesis occurs primarily in
red bone marrow (myeloid tissue), which is found in the upper end
of the long bones humerus and femur; flat bones such as the
sternum, ribs and cranial bones; and vertebrae and pelvic bones.
     In general, "stem cells" are precursor cells, cells that
have not yet differentiated into specialized cells. The early
embryo consists mostly of stem cells. A "totipotent stem cell" is
a stem cell that has the capacity to differentiate into any kind
of tissue cell; a "pluripotent stem cell" is a stem cell that has
the capacity to differentiate into several different kinds of
tissue cell.
     The primary cells that give rise to differentiated blood
cells are called hematoblasts (hemocytoblasts; pluripotent
hematopoietic stem cells), and they reside primarily in red bone
marrow, although some primary stem cells do circulate in the
blood. Five different types of secondary precursor blood cells
develop from these primary stem cells: erythroblasts,
myeloblasts, monoblasts, lymphoblasts, megakaryoblasts.
     Hematoblasts, the primary stem cells of all blood cell
types, were first discovered and named in the 1870s. Credit for
the discovery of hematoblasts is usually given to the noted
French hematologist Georges Hayem (1841-1933) (sometimes called
the "father of hematology"), but now there is evidence that Hayem
was not the discoverer of hematoblasts, that Hayem was not even
the first to name these primary blood stem cells "hematoblasts",
and that Hayem in fact may have lifted the name "hematoblast"
from an earlier paper announcing the discovery of primary blood
stem cells published by the German pathologist and medical
illustrator Carl Heitzmann (1836-1896).
... ... Stella Fatovic-Ferencic (Croatian Academy of Sciences,
HR) presents a report on the history of the discovery of
hematoblasts, the author making the following points:
     1) The author points out that the development of hematology
began in the second half of the 19th century, primarily with Paul
Ehrlich (1854-1915), whose demonstration of the staining
characteristics of white blood cells with aniline dyes in 1877
(while he was still a student) began the serious categorization
of the varieties of blood cells. Hayem's technique of vital
staining of blood cells was introduced shortly afterwards, and
Hayem is usually quoted in the medical handbooks, manuals, and
dictionaries of the period as having discovered the
"hematoblast". Hayem's popular textbook on diseases of the blood
was published in 1878. A year before that, in 1887, Hayem
published a paper in the proceedings of the French National
Academy of Sciences (Acad. Sci. Compt. Rend. 1877 85:907) with
the title "On the evolution of red cells in the blood of
oviparous vertebrates", and in this paper Hayem states as
follows: "The blood of oviparous vertebrates (birds, reptiles,
frogs, fish) invariably contain colorless cells that are
essentially different from white blood cells. These elements,
during progressive development, become mature red cells, and for
this reason I propose they be called hematoblasts. I have noted
their presence in all the oviparous vertebrates that I have
examined (various birds, turtles, lizards, snakes, frogs, toads,
tritons, axolotls, various fishes). One equally finds them in the
blood of the tadpole of the frog, where they have the same
characteristics as those of the adult animal." [Translation from
the French by ScienceWeek.]
     2) The author (Fatovic-Ferencic) points out that 5 years
before Hayem's article appeared, hematoblasts were described in
depth and also called such by Carl Heitzmann in a paper published
in Vienna in 1872 (Med. Jahrbuch. 1872 p. 341-366). In this
paper, Heitzmann describes blood cells in bone marrow obtained
from a dog, mentions various types of immature and mature blood
cells, and also points out that these various cells represent
different phases of evolution of red blood cells. Heitzmann
states: "Since I will have the chance to speak of these
(cellular) formations repeatedly (in this text), I want to
prevent reiterating their description and choose for them the
name hematoblasts." [Translation from the German by Fatovic-
Ferencic.] Heitzmann's text includes a description of a staining
procedure for hematoblasts. At the time of the publication of his
paper on hematoblasts in 1872, Heitzmann was an associate
professor and a candidate for the chair of pathology at the
University of Vienna. Heitzmann did not receive the post, and in
1874, three years before the publication of Hayem's paper on
hematoblasts, he left Europe for the US, where he founded the
American Dermatological Association in 1876.
     3) The author (Fatovic-Ferencic) points out that it is clear
that Heitzmann's description and use of the term "hematoblasts"
was published 5 years before the paper by Hayem appeared. The
descriptions and conclusions of both authors were very similar.
The term "hematoblast" was used by both authors, "a fact which is
rather difficult to explain. There is also the possibility that
Hayem had read Heitzmann's article on the hematoblast and used
the term without quoting Heitzmann."
     4) The author points out that Hayem was named a titular
professor when he was only 45. In contrast, Heitzmann's
scientific achievements were never recognized and he never
received the title "professor". While Hayem became an honored and
respected scientist, Heitzmann did not succeed to the chair of
pathology at the University of Vienna, and he left disappointed
for New York, where he trained scores of young doctors.
"Heitzmann died as he lived, moving from one place to another and
finally succumbed to a heart attack in Rome at the age of 60."
The author concludes: "We owe [Heitzmann] some revisions. His
research provided an excellent base for future investigators in
the fields of dermatology, hematology, and immunology, and these
efforts must not be forgotten."
-----------
Stella Fatovic-Ferencic: The discovery of the hematoblast by Carl
Heitzmann (1836-1896) in 1872.
(Int. J. Dermatology 2000 39:632)
QY: Stella Fatovic-Ferencic: stella@hazu.hr
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 25May01
For more information: http://scienceweek.com/swfr.htm

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7. IN FOCUS: ON THE MYTH OF THE MIRACLE OF GENIUS
"Try to answer these questions: What five-letter word do all
college graduates spell wrong? How is it possible that our
basketball team won a game last week by the score of 73-49, and
yet no one man on the team scored as much as a single point? How
can it be that a man in a certain town in the United States
married 20 women from the town, yet he broke no law, he is not a
Mormon, and they are all still alive? If you answered W-R-O-N-G
for the first question, that the basketball team was an all-
woman's team for the second question, or that the man is a
minister for the third question, you likely experienced what is
called the "aha" reaction of insight into problem solving. This
is one theory of genius -- the answer inexplicably pops into the
ingenious mind from on high, a mental miracle from the muses.
Einstein stumbles onto relativity theory while dreaming of riding
on a beam of light. Kekule discovers the structure of the benzene
ring by dreaming of a snake biting its tail. Darwin suddenly
becomes an evolutionist while visiting the Galapagos Islands.
Wallace discovers natural selection while in a feverish fit of
malaria in the Malay Archipelago. Evarist Galois, out of fear of
a foreshortened life, pens the entirety of his mathematical group
theory the night before he was killed in a duel over a woman.
Newton flashes into universal gravitation when beamed by an
apple. Coleridge creates his brilliant poem "Kubla Khan" one
afternoon during an opium-induced altered state of consciousness.
And, perhaps best known of all, Mozart composes perfect
symphonies on first draft -- no corrections, additions, or
deletions needed -- a miraculous masterpiece. The only problem
with this scenario of the development of genius is that none of
these stories are true."
-----------
Michael Shermer: _The Borderlands of Science: Where Sense Meets
Nonsense_
(Oxford University Press, Oxford UK 2001, p.262)
http://www.amazon.com/exec/obidos/ASIN/0195143264/scienceweek
-------------------
SCIENCE-WEEK http://scienceweek.com 25May01

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8. FROM THE SCIENCEWEEK ARCHIVE:
ASTRONOMY: ON THE EFFECTS OF ASTEROID-EARTH IMPACTS
During the past several years, there has been much media
attention devoted to the prospect of an asteroid impacting Earth.
Such impacts were apparently more common several billion years
ago than at present, but impacts are definitely possible at any
time, and the US National Aeronautics and Space Agency (NASA) has
in place a program to detect all near-Earth asteroids larger than
approximately 1 kilometer in radius. But if we do detect a large
asteroid on a collision-course with Earth, it is not yet clear
what we can do about it with our present technology except
perhaps engineer a nuclear missile hit to deflect it.
... ... Jack J. Lissauer (NASA Ames Research Center, US) presents
the following considerations concerning the expected effects of
asteroid impacts on Earth and life on Earth:
     1) The largest mass extinction of the past 200 million years
occurred 65 million years ago, when approximately half of the
genera of multicellular organisms on Earth, including all of the
dinosaurs, suddenly died off. The geological record indicates
that a layer of impact-produced minerals and the element iridium
(an element rare in the crust of the Earth but more abundant in
primitive meteorites) was deposited at the time the dinosaurs
vanished -- the so-called Cretaceous/Tertiary or K/T boundary. In
addition to this, the largest known crater on Earth to be dated
at less than 1 billion years old was apparently formed at this
time. Taken together, these data imply that the K/T mass
extinction was caused by the impact into the Yucatan peninsula of
an asteroid or comet of approximately 10 kilometers in radius.
[*Note #1].
     2) The author presents the following tabulation of the
effects of impacts of objects of various sizes on the Earth and
on life on Earth:
... ... a) Super colossal object (radius > 2000 kilometers):
Melts the planet; drives off all volatiles and wipes out life on
the planet.
... ... b) Colossal object (radius > 700 kilometers): Melts the
crust; wipes out life on planet.
... ... c) Huge object (radius > 200 kilometers): Vaporizes
oceans; life may survive below the surface.
... ... d) Extra large object (radius > 70 kilometers): Vaporizes
upper 100 meters of oceans; pressure-cooks photic zone; may wipe
out photosynthesis.
... ... e) Large object (radius > 30 kilometers): Heats
atmosphere and surface to approximately 1000 kelvins; continents
cauterized.
... ... f) Medium object (radius > 10 kilometers): Fires, dust,
darkness; atmosphere/ocean chemical changes; large temperature
swings; half of living species extinct.
... ... g) Small object (radius > 1 kilometer): Global dusty
atmosphere for months; photosynthesis interrupted; individual
deaths but few species become extinct; civilization threatened.
... ... h) Very small object (radius > 100 meters): Major local
effect; minor hemispheric effects; dusty atmosphere; only minor
global effects on life.
-----------
Jack L. Lissauer: How common are habitable planets?
(Nature 2 Dec 99 402supp:C11)
QY: Jack L. Lissauer [lissauer@ringside.arc.nasa.gov]
-----------
Text Notes:
... ... *Note #1: Some authors (see below) have stated the
Yucatan impactor had a diameter of 10 kilometers rather than a
radius of 10 kilometers.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 14Jan00
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
ON THE IMPACT HAZARDS OF ASTEROIDS
G. Verschuur (University of Memphis, US) reviews the
probabilities and consequences of asteroid collisions with Earth.
Our civilization has just passed through an extraordinary era of
scientific discovery that has brought with it the awareness that
planet Earth is profoundly vulnerable to devastating cosmic
collisions. In recent years, the evidence that mass extinctions
of life on Earth can be attributed to the consequences of comet
or asteroid impacts has become overwhelming. Most famous among
such catastrophes is the Cretaceous-Tertiary impact that
apparently marked the demise of the dinosaurs about 65 million
years ago. The attention of many planetary scientists has turned
to the problem of assessing the likelihood that our civilization
may be threatened by a rogue comet or asteroid in the near
future. Asteroid hunters estimate that 9000 objects of dimensions
0.5 kilometers or larger are in near-Earth orbits, and that of
these only 350 have been identified to date. A small-to-medium
size 200 meter object smashing into a 5-km deep ocean at 50 km
per second would raise a splash 35 kilometers high in 40 seconds
and produce tsunamis that would inundate lands bordering the
ocean. Calculations indicate that the impact anywhere on Earth of
even a medium-size asteroid 0.2 to 1.0 km would be catastrophic.
The author suggest that we have been lucky to avoid a recent 
catastrophic collision with a comet or asteroid, and that
although it may not happen in the next year or the next century,
eventually the Earth *will* be hit by a sizable piece of cosmic
debris. QY: Gerrit L. Verschuur, Univ. of Memphis 901-678-2169.
(Sky & Telescope June 1998) (Science-Week 1 May 98)
-------------------
Related Background:
ISOTOPIC EVIDENCE FOR THE CRETACEOUS-TERTIARY IMPACTOR
The Cretaceous period is the geological period ranging
approximately from 146 million years ago to 65 million years ago,
and was apparently characterized towards its end by the rapid
extinction of a number of species, including the dinosaurs. There
have been five major extinctions according to the fossil record,
the Cretaceous extinction one of them, and the consensus is that
these extinctions were related to violent geophysical events,
perhaps asteroid impacts. The Chicxulub impact crater in the
Yucatan peninsula of Mexico is a large impact crater apparently
caused by a 10 kilometer-diameter asteroid, the impact area
extending at least 100 kilometers from the impact center. Using
Argon(40)/Argon(39) isotope dating methods, this impact crater
has been dated with high precision at 64.98 million years ago,
which places the impact at the end of the Cretaceous, and the
most popular current hypothesis to explain the Cretaceous
extinction is the global effect of the Chicxulub impact on the
extant life forms. This hypothesis was first proposed by Luis and
Walter Alvarez in the 1970s on the basis of non-terrestrial dust
of presumed cosmic origin in deposits at the K/T boundary, but
the Yucatan crater was unknown at that time and was not
discovered until the 1990s. But direct isotope evidence of an
impactor is still missing, and some researchers have argued that
high concentrations of iridium and other noble metals in K/T
boundary sediments, the basis for the K/T impactor hypothesis,
can be explained by enhanced volcanic activity that occurred near
the end of the Cretaceous, bringing up noble metals from Earth's
mantle, which similar to meteorites has high concentrations of
noble metals. ... ... A. Shukolyukov and G.W. Lugmair now report
a high-precision *mass spectrometric analysis of chromium in
sediment samples from the K/T boundary confirms the cosmic
origins of the K/T phenomenon. The authors report that the
isotopic composition of chromium in K/T boundary samples from
Stevns Klint, Denmark, and Caravaca, Spain, is different from
that of Earth and indicates its extraterrestrial source. The
authors suggest the chromium isotope signature is consistent with
a *carbonaceous chondrite-type impactor, and that the observed
differences in the chromium isotopic composition among the
various meteorite classes can serve as a diagnostic tool for
deciphering the nature of impactors that have collided with Earth
during its history.
-----------
A. Shukolyukov and G.W. Lugmair (Univ. of Calif. San Diego, US)
Isotopic evidence for the Cretaceous-Tertiary Impactor and its
Type.
(Science 30 Oct 98 282:927)
QY: A. Shukolyukov, Univ. of Calif. San Diego 619-534-2230.
-----------
Text Notes:
... ... *mass spectrometric analysis: The mass spectrometer is a
device in which molecules are ionized and the accelerated ions
are separated according to their mass to charge ratio. The
relative abundance of isotopes or other ionized species can thus
be determined by measuring positive or negative ion currents.
... ... *carbonaceous chondrite: "Stony" meteorites (aerolites)
are meteorites formed solely of rock-forming silicates, and
chondrites are a type of stony meteorite consisting of an
agglomeration of millimeter-sized globules (chondrules) that are
thought to be unchanged since the original condensation out of
the nebula from which the sun and solar system formed. A
carbonaceous chondrite is a chondritic meteorite that contains a
relatively large amount of carbon, with a resultant dark
appearance.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 27Nov98
-------------------
Related Background:
ON METEORITE IMPACT AND THE K/T MASS EXTINCTION
... In a short review of the meteorite impact hypothesis and the
K/T extinction, K.O Pope et al make the following points: 1)
Confirmation of the impact portion of the Alvarez hypothesis
marks a turning point in the study of the K/T mass extinction, a
turning point away from speculations about possible causes and
toward linking the extinctions to a single catastrophic event. 2)
Advances in computer modeling of the impact, coupled with
knowledge of the target rocks and their behavior under the
high-pressure shock, have shed light on what happened during the
first few seconds after impact. A key aspect of the Yucatan site
is that the upper 3 kilometers of rock were rich in water,
carbonate, and sulfate, which upon impact produced about 200
gigatons each of SO(sub2) and H(sub2)O vapor and other gases that
greatly altered the properties of the stratosphere. 3) Early work
predicted that smoke and dust from the impact plunged the Earth
into a freezing blackout. Recent computer simulations and
atmospheric models indicate that within a few weeks to months
temperatures and light levels would have begun to rebound due to
the release of heat stored in the oceans and the coagulation and
fall of the dust and soot. The major effects of the dust and soot
would last about 1 year or less, but SO(sub2) and water vapors
would remain in the stratosphere and ultimately produce sulfuric
acid aerosols. Models indicate that a global aerosol cloud would
be continuously produced for approximately 12 years, blocking out
over 50 percent of the sunlight during the first 10 years. The
authors conclude: "Now that we have a better understanding of the
dynamics of the impact, gleaned from the discovery of the crater
and the studies that followed, we can begin to address a wide
range of complex global effects. There is much work ahead, but
the course is clear."
-----------
K.O. Pope et al (3 authors at 3 installations, US)
Meteorite impact and the mass extinction of species at the
Cretaceous/Tertiary boundary.
(Proc. Natl. Acad. Sci. US 15 Sep 98 95:11028)
QY: Kevin O. Pope, Geo Eco Arc Research, 2222 Foothill Blvd., La
Canada, CA 91011 US.
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 23Oct98
-------------------
Related Background:
ANALYSIS OF THE CHICXULUB IMPACT CRATER
... An important parameter of the [Chicxlulub] impact is the
total area of the impact crater, since that area would be related
to the amount of debris thrown into the atmosphere. Until now,
the usual figure for the largest dimension of the impact crater
has been approximately 300 kilometers. Morgan et al (20 authors
at 8 installations, UK US MX CA) now report an analysis of
seismic data of the Chicxulub impact, determining the diameter of
the transient cavity at about 100 kilometers. The authors suggest
this parameter is critical for constraining any proposed
impact-related effects on the Cretaceous environment, and that
the seismic data indicate the morphology of the crater is similar
to large impact structures observed on other planets such as
Venus.
QY: Mike Warner: m.warner@ic.ac.uk
(Nature 4 Dec 97) (Science-Week 26 Dec 97)


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