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.

January 7, 2000 -- Vol. 4 Number 1

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Most people in the world thrive on certainty and
an absence of puzzlement, which brings to them
mental comfort and security. Scientists, on the other hand,
thrive on doubt and the existence of natural puzzles,
which brings to them energy and an urge to find answers.
Doubt and a joy in solving puzzles are the main engines
in the practice of science.
-- Julian Tobias (1911-1964)

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Contents of This Issue:

1. Foundations: 1932 -- the Year of Physics
2. Planetary Science: Porous Asteroids and Planet Formation
3. Cell Biology: A Physical Analysis of Ciliary Beating
4. Cell Biology: On the Significance of Intracellular Circulation
5. Neurobiology: On the Stability of Fast-Synapse Receptors
6. Anthropology: Genomic Analysis of Human History
 
In Focus: Neutrinos and Observational Astronomy

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

1. FOUNDATIONS: 1932 -- THE YEAR OF PHYSICS
Identification of important discoveries in science is easier in
the long-run than in the short-term, principally because
consequences and influences of a discovery accumulate over
decades, and the most important discoveries acquire obvious
accumulations. The 20th century has been a phenomenal time for
physics, with important discoveries made nearly every year. In an
essay, H.G.B. Casimir (b. 1909), whose career in physics spans
almost the entire 20th century, chooses 1932 as an "annus
mirabilis" in physics. Casimir identifies four major discoveries
by physicists in 1932: the neutron, heavy hydrogen, nuclear
reactions, and the positron. But heavy hydrogen, in fact, was
discovered by a chemist, Harold C. Urey (1893-1981), who never
called himself other than a chemist, and who received the Nobel
Prize for Chemistry in 1934 for his discovery. Casimir implies
that the discovery of heavy hydrogen (and the "deuteron" nucleus)
followed easily from the discovery of the neutron by James
Chadwick (1891-1974), but Urey actually made his discovery of
heavy hydrogen in late 1931, before the results of Chadwick's
famous experiment were obtained. Leaving aside these historical
refinements, we note the following points made by Casimir:
     1) Ernest Rutherford (1871-1937) postulated the existence of
the neutron, a particle without electric charge and approximately
the same mass as the proton. The neutron was discovered in 1932
by James Chadwick, who created beams of neutrons by irradiating
beryllium with alpha particles. The result of this experiment was
that it quickly became clear that atomic nuclei were composed of
protons and neutrons, and were not a medley of protons, "nuclear
electrons", alpha particles, etc., the medley that was considered
the consensus model of the atomic nucleus between 1920 and 1932.
The Chadwick experiment was indeed a major breakthrough in atomic
physics. Chadwick received the Nobel Prize for Physics in 1935.
     2) Casimir says only the following about the discovery of
heavy hydrogen: "[After Chadwick's experiment] nuclei were
henceforth regarded as compounds of protons and neutrons. The
simplest case is one proton and one neutron. This particle was
called deuteron, D. Its oxide, D(sub2)O is the molecule of heavy
water. It was found in 1932 that about one part in six thousand
of normal water is heavy water." [Editor's note: Strangely,
Casimir does not mention Urey at all. Urey's discovery of heavy
hydrogen is a classic illustration of how a simple experiment can
yield extraordinarily important results. Urey began working on
heavy hydrogen in 1931, when it was already suspected by chemists
that hydrogen had a heavy isotope. Reasoning that liquid hydrogen
composed of the lighter hydrogen should evaporate before liquid
hydrogen composed of the more massive heavy hydrogen, Urey slowly
evaporated 4 liters of liquid hydrogen down to 1 cubic centimeter
and then investigated the spectrum of the remnant. He found the
ordinary absorption lines of hydrogen were accompanied by faint
lines in the exact positions later predicted by theory for heavy
hydrogen. The name "deuterium" was given to the heavy isotope.
After Urey's discovery, Chadwick and others in his laboratory
investigated the structure of the deuteron and demonstrated that
it consisted of one proton and one neutron.]
     3) In 1932, John Cockcroft (1897-1967) and Ernest Walton
(1903-1995) used a 700-kilovolt high-voltage generator to
accelerate protons against lithium atoms and demonstrate that
these lithium atoms "broke in two". Cockcroft and Walton
announced they had "split the atom", and "so began the era of big
machines." Casimer states: "The high voltage generators were
succeeded by cyclotrons, the cyclotrons by even more powerful
apparatus." Cockcroft and Walton received the Nobel Prize for
Physics in 1951. [Editor's note: Here again, Casimir's account
requires some modification: The first "cyclotron" was built and
used experimentally and named in 1930 by Ernest O. Lawrence
(1901-1958), well before the Cockcroft-Walton experiment. Larger
and larger cyclotrons were indeed built during the following
decades. Concerning the "splitting of atoms", an argument can be
made that Rutherford had already done so before 1920. Rutherford
had certainly driven protons out of nitrogen atoms by bombarding
the atoms with alpha particles.]
     4) In 1932, Carl D. Anderson (1905-1991) discovered the
positron, whose existence was predicted by the theoretical
physicist Paul A.M. Dirac (1902-1984). The positron is the
antiparticle of the electron. It has a charge identical but
opposite to that of the electron, and a rest mass identical to
that of the electron. Anderson received the Nobel Prize for
Physics in 1936. Casimir points out that the positron was the
first short-lived particle to be "created out of empty space" --
a prelude to the high-energy physics that blossomed beginning in
1950, and the powerful machines that now reveal the existence of
"whole families of short-lived particles, many of them predicted
by theory." Casimir concludes: "Sometimes it almost appears that
the theories are not a description of a nearly inaccessible
reality, but that so-called reality is a result of the theory."
-----------
H.B.G. Casimir: Annus physicalis 1932.
(Nature 2 Dec 99 402:463)
QY: H.B.G. Casimir, De Zegge 7, 5591 TT Heeze, NL.
-------------------
Summary by SCIENCE-WEEK [http://scienceweek.com] 7Jan00
[For more information: http://scienceweek.com/search/search.htm]


2. PLANETARY SCIENCE: POROUS ASTEROIDS AND PLANET FORMATION
Asteroids (also called "minor planets") are small rocky objects,
most of which orbit the Sun in a belt between the orbits of Mars
and Jupiter. A few asteroids follow orbits that bring them into
the inner Solar System, and several asteroids occasionally pass
within a few tens of millions of miles of Earth. Some asteroids
are located in the orbit of Jupiter, and some asteroids have been
detected as far away as the orbit of Saturn. Concerning asteroids
in general, approximately 200 of these objects are more than 100
kilometers (60 miles) in diameter, and more than 2000 asteroids
are more than 10 kilometers in diameter. There are believed to be
approximately half a million asteroids with diameters greater
than 1 kilometer. The consensus view is that asteroids are
composed of material that failed to build a planet at a distance
of 2.8 *astronomical units (AU) from the Sun, perhaps due to the
influence of massive Jupiter just outside the asteroid belt
[*Note #1]. Until recently, the shapes and surface features of
asteroids were a matter of conjecture; during the past decade,
however, significant direct observations of asteroids have been
relayed back to Earth from spacecraft.
... ... Erik Asphaug (University of California Santa Cruz, US)
presents a review of current research on the geology of
asteroids, the author making the following points:
     1) The dominant geological process affecting asteroids is
collision with other asteroids, most of these collisions
producing craters formed when material is blown explosively from
the impact site. The most violent collisions are catastrophic and
produce families of smaller asteroids. At lower impact
velocities, colliding asteroids can merge, and this is relevant
for an understanding of the formation of planets from the swarm
of *planetesimals (proto-asteroids) in the early Solar System.
Because catastrophic collisions and cratering reduce the mass of
an asteroid, one research problem has been to provide an
explanation of the survival of asteroids and a description of how
planetesimals could have accumulated into planets.
     2) All known apparent asteroid densities are quite low,
suggesting these bodies are porous. This porosity might be due to
a fragmented internal structure or to a structure consisting of
loosely bound piles of material. Many asteroids have giant
craters which are half their total size or larger, and since
craters of that size cannot form in solid rock without shattering
the parent body to pieces, their existence has been a puzzle.
     3) Computer models and laboratory experiments have
demonstrated that because a composite asteroid transmits impact
energy so poorly, it is much more difficult to break up than a
monolithic asteroid, so the internal composition and structure of
an asteroid are important factors determining the effect of a
collision.
     4) A recent hypothesis by Housen et al (2 installations,
US), based on experimental data and dimensional analysis
(scaling) arguments, suggests that highly porous asteroids might
accumulate rather than lose mass during collisions. These authors
show that giant craters could be formed by compression of a
highly porous target, rather than as a result of ejected
material. Thus, high porosity might be a transient feature of
certain asteroids, which become more dense with each impact. This
is good news for researchers who model planet formation and who
need a mechanism for planetesimal mass accumulation. But it is
bad news for planners of protection of the Earth against asteroid
impacts, because the implication is that instead of an asteroid
on a collision course with Earth being diverted or fragmented by
a missile, the asteroid could simply absorb explosive energy.
-----------
Erik Asphaug: Survival of the weakest.
(Nature 11 Nov 99 402:127)
QY: Erik Asphaug [asphaug@earthsci.ucsc.edu]
-----------
K.R. Housen et al: Compaction as the origin of the unusual
craters on the asteroid Mathilde.
(Nature 11 Nov 99 402:155)
QY: Kevin R. Housen [kevin.r.housen@boeing.com]
-----------
Text Notes:
... ... *astronomical units (AU): 1 AU = the mean distance from
the Sun to the Earth = approximately 93 million miles, and
exactly 149,597,870 kilometers.
... ... *Note #1: The figure "2.8" is based on Bode's law
(Titius-Bode law), an intriguing relationship between the
distances of the planets from the Sun, named after Johann Titius
(1729-1796) (who formulated the law in 1766) and Johann Bode
(1747-1826) (who published the law in 1772). Take the sequence
0,3,6,12,24,..., where each number (except the 3) is twice the
previous number, add 4 to each number and divide by 10. The
resulting sequence (0.4, 0.7, 1.0, 1.6, 2.8, 5.2,...) is in good
agreement with the actual distances in astronomical units of most
planets, provided that the asteroids are included and considered
as one entity at a mean distance of 2.8 AU. Although the law
fails to predict the correct distances for Neptune and Pluto,
some researchers believe the law may have some significance with
respect to the formation of the Solar System. The law did predict
the distances of the 6 planets known by Titius and Bode, and led
Bode to predict the existence of an undiscovered planet between
Mars and Jupiter.
... ... *planetesimals (proto-asteroids): Planetesimals are
bodies with dimensions of 10^(-3) to 10^(3) meters that are
believed to form planets (or asteroids) by a process of
accretion. The term "accretion" refers to an aggregation, an
increase in the mass of a body by the addition of smaller bodies
that collide and adhere to it, provided the relative velocities
are low enough for coalescence. As the mass of the agglomerate
increases, so does the rate of accretion, and this accretion
process is believed to generally occur in a disk of debris
surrounding a star (stellar accretion disk), the disk a swarm of
dust grains that evolve into planetesimals and then planets. 
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 7Jan00
[For more information: http://scienceweek.com/search/search.htm]
-------------------
Related Background:
DISCOVERY OF A MOON ORBITING AN ASTEROID
The possibility that some asteroids have satellites (moons) has
been debated since the 1970s, when observers reported anomalous
generally unconfirmed "additional" events during *occultations of
bright stars by asteroids, with these events sometimes
interpreted to be caused by unseen companions. Asteroidal
satellites have been suspected from unusual light curves, slow
rotation rates, and double impact craters on planetary surfaces.
The estimated prevalence of such satellites, inferred
observationally and theoretically, ranges from common to uncommon
to essentially absent. Theory indicates that stable orbits for
asteroidal satellites can indeed exist, even in the presence of
Solar or Jovian perturbations. The first asteroidal satellite to
be actually found was the satellite Dactyl orbiting the asteroid
Ida, discovered during the flyby of the Galileo spacecraft in
1993. Since then, modeling of the catastrophic, collisional
formation, tidal evolution, and longevity of asteroidal
satellites suggests that such satellites may be common, and
evidence for such moons has been sought with some effort because
the relative frequency of such satellites will bear on ideas
concerning the  collisional history of the asteroid belt and the
Solar System.
... ... W.J. Merline et al (10 authors at 9 installations, US DE
FR) now report the discovery of a satellite of the asteroid 45
Eugenia using a special optical system on a ground-based
telescope. The authors report the satellite has a diameter of
approximately 13 kilometers, and an orbital period  of
approximately 4.7 days, with an orbital radius of 1190
kilometers.
-----------
W.J. Merline et al: Discovery of a moon orbiting the asteroid 45
Eugenia.
(Nature 7 Oct 99 401:565)
QY: W.J. Merline [merline@boulder.swri.edu]
-----------
Text Notes:
... ... *occultations: The term "occultation" refers to the
temporary cutting off of the light from one celestial body as
another and nearer body passes in front of it.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 26Nov99
[For more information: http://scienceweek.com/search/search.htm]
-------------------
Related Background:
GROUNDBREAKING OBSERVATIONS OF SMALLEST SOLAR SYSTEM ASTEROID
Asteroid 1998 KY26, discovered last year, is considered the
smallest Solar System object ever studied in detail. The 30-meter
object passed 800,000 kilometers from Earth in the period June
2-8, 1998. A report of observations of the asteroid will be
published in the journal _Science_ this week by S.J. Ostro et al.
Ostro is quoted as saying, "Enormous numbers of objects this
small are thought to exist very close to Earth, but this is the
first time we've been able to study one in detail. Ironically,
this asteroid is smaller than the radar instruments we used to
observe it." The asteroid is spinning with a rotation period
calculated at 10.7 minutes, compared to rotation periods of at
least several hours for the approximately 1,000 asteroids
measured to date. In addition to these findings, the minerals in
1998 KY26 are believed to probably contain approximately 1
million gallons of water. Ostro says, "This asteroid is quite
literally an oasis for future space explorers. Its optical and
radar properties suggest a composition like carbonaceous
chondrite meteorites, which contain complex organic compounds
that have been shown to have nutrient value. These could be used
as soil to grow food for future human outposts. And among the
25,000 or so asteroids with very reliably known orbits, 1998 KY26
is in an orbit that makes it the most accessible to a
spacecraft."
(NASA 22 Jul 99) (Science-Week Bulletin 23 July 99)
-------------------
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:
ASTEROID DISCOVERED TO HAVE ORBIT LOCKED TO EARTH'S
This week came the interesting news of a 5 km asteroid whose
orbit is dynamically locked into the orbit of the Earth, making
it, aside from the Moon, Earth's only known natural companion.
An explanation of the quite special orbital geometry is difficult
without diagrams, but one can attempt it. The story is that
more than two hundred years ago, the French mathematician
Lagrange investigated the dynamics of the gravitational three-
body problem, and discovered that if there are two bodies, A and
B, and the mass of B is less than 0.04 the mass of A, then as B
orbits around A, there are two equilibrium points in B's orbit,
one leading B and one trailing B, and that at these equilibrium
points a third smaller body (or bodies) can enter the two-body
system and there can be sustained a dynamic equilibrated
arrangement. Such arrangements have in fact been observed for
asteroids associated with the Jupiter and Mars orbits. This new
asteroid, called asteroid 3753, is associated with Earth's orbit,
but in a quite special way: the orbit of 3753 encompasses both
equilibrium points and is a "horseshoe" orbit, and it is only
because the asteroid's orbit is highly inclined with respect to
the plane of the Earth's orbit that a collision is unlikely. The
analysis and numerical solutions of the relevant dynamical
equations were presented by Paul A. Wiegert et al (York
University, CA; University of Turku, FI).
(Nature 12 Jun 97) (Science-Week 19 Jun 97)
[For more information: http://scienceweek.com/search/search.htm]


3. CELL BIOLOGY: A PHYSICAL ANALYSIS OF CILIARY BEATING
The structural framework ("cytoskeleton") of eukaryotic cells
(cells with nuclei and other membrane-bound internal structures)
consists of an arrangement of macromolecular structures:
microtubules, intermediate filaments, and microfilaments. The
microtubules are hollow cylinders about 24 nanometers in
diameter, many microns in length, and consist of heterodimers of
alpha- and beta-tubulin proteins plus a variable set of other
proteins. They form the scaffolding of the mitotic spindle (an
important structure in cell division), organize other cytoplasmic
structures, and are the structural core of various organelles
involved in cell movement (cilia and flagella). Cilia and
flagella are motile membrane-enclosed appendages that project
from the surface of certain types of cells. Depending on the cell
type involved, these motile appendages perform one of two
alternative functions: 1) cells that are firmly anchored in place
use ciliary motion to move fluids across their surfaces; and 2)
cells that are not anchored, such as sperm cells or unicellular
organisms, use the movement of cilia or flagella to propel
themselves through the fluid medium in which they are suspended.
Although cilia and flagella are closely related structures, they
can be distinguished from each other on the basis of differences
in size, number, and pattern of movement. Cilia are much shorter
than flagella, usually approximately 5 to 10 microns in length,
more numerous on any particular cell surface, and move in a
complex patter whose net result is to propel fluid across the
cell surface. In this context, the term "metachronal rhythm"
refers to a pattern of ciliary movement (ciliary beating) in
which each cilium is at a slightly different stage in the beat
cycle from those on either side of it, the result a smooth
progression of waves of beating along the units. At the molecular
level, the present consensus is that ciliary movement is produced
by microtubules sliding past one another (rather than by
microtubules contracting), and that this microtubule sliding is
in turn produced by the motor protein dynein, which has been
identified as comprising specific protrusions in the form of
"dynein arms" in the internal structure of the cilium. The
transient attachments and movements of various dynein arms in a
single cilium are evidently highly coordinated to produce precise
bending and movement of the cilium. At the present time,
delineation of the detailed internal structure of cilia and the
role of dynein arms in ciliary movement are the focus of research
in a number of laboratories.
... ... S. Gueron and K. Levit-Gurevich (2 installations, IL)
present a quantitative study of the energy expenditure of beating
cilia and of the energetic significance of metachronism. The
authors report the following:
     1) The internal mechanism of cilia is among the most ancient
biological motors on an evolutionary scale, producing beat
patterns that consist of 2 phases: a) during the effective
stroke, the cilium moves approximately as a straight rod, and b)
during the recovery stroke, the cilium rolls close to the surface
in a tangential motion. It is commonly agreed that these 2 phases
produce efficient functioning: the effective stroke encounters
strong viscous resistance and generates thrust, whereas the
recovery stroke returns the cilium to the starting position while
avoiding viscous resistance.
     2) Metachronal coordination between cilia, which occurs when
many cilia beat close to each other, is believed to be an
autonomous result of the hydrodynamical interactions of the
system. Qualitatively, metachronism is perceived as a mechanism
for reducing the energy expenditure required for beating.
     3) The authors developed a method for computing the work
done by model cilia that beat in a viscous fluid. The theoretical
framework used by the authors consists of 3 building blocks
linked together: a) a hydrodynamic description of the ciliary
system; b) geometric equations for the motion of the cilia; c) a
model internal bend-generating mechanism.
     4) The authors report that for a single cilium beating in
water, the mechanical work done during the effective stroke is
approximately 5 times the amount of work done during the recovery
stroke. Investigation of multicilia configurations indicates that
having neighboring cilia beat metachronally is energetically
advantageous and "perhaps even crucial for multiciliary
functioning." Finally, the authors report the use of the model to
approximate the number of dynein arm attachments that are likely
to occur during the effective and recovery strokes of a beat
cycle, the model predicting that almost all of the available
dynein arms should participate in generating the motion.
-----------
S. Gueron and K. Levit-Gurevich: Energetic considerations of
ciliary beating and the advantage of metachronal coordination.
(Proc. Natl. Acad. Sci. US 26 Oct 99 96:12240)
QY: Shay Gueron [shay@math.haifa.ac.il]
-------------------
Summary by SCIENCE-WEEK [http://scienceweek.com] 7Jan00
[For more information: http://scienceweek.com/search/search.htm]
-------------------
Related Background:
MOTOR PROTEINS: DYNEIN ARMS AS FORCE GENERATORS
"Motor proteins" are mechanico-chemical enzymes involved in
locomotion of cells or transport of materials in cells, and there
are three families of such proteins: kinesins, dyneins, and
myosins. Kinesins and dyneins are microtubule based motor
proteins, while myosin is a microfilament based motor protein. In
general, as mechanico-chemical enzymes, motor proteins convert
energy from hydrolysis of nucleotides to mechanical force, and
since they are involved in many important cellular events, the
molecular details are currently the focus of intensive research.
Many eukaryotic cells (cells that have membrane-bound organelles
such as a cell nucleus) have flagella, long whip-like structures,
that beat rhythmically. The central core of the flagellum is
called the "axoneme", and it consists of a regular array of
microtubules (see background material in previous report). The
motor protein dynein is known to power flagellar motion,
suggesting that oscillation may be inherent in this protein.
... ... Shingyoji et al (5 authors at 4 installations, JP)
report an attempt to determine whether oscillation is a property
of dynein arms themselves, or whether oscillation requires an
intact axoneme. Using *optical trapping nanometry, the authors
measured the force generated by a few dynein arms on an isolated
doublet microtubule. When the dynein arms on the doublet
microtubule contact a singlet microtubule and are activated by
photolysis of adenosine triphosphate (ATP), they generate a
force that moves the singlet microtubule over the perpendicular
doublet in a processive manner, the force and displacement in
oscillation, with the maximum frequency of the oscillation
dependent on ATP concentration. The authors suggest that
oscillation of dynein arms may be a basic mechanism underlying
flagellar beating, and that their results may be important not
only for understanding the mechanism of flagellar beating, but
also for understanding the functions of motor proteins in
general.
QY: Chikako Shingyoji (chikako@biol.s.u-tokyo.ac.jp)
(Nature 18 Jun 98 393:711) (Science-Week 10 Jul 98)
-------------------
Related Background:
... ... *optical trapping nanometry: The term "optical trapping"
refers to the confinement of (microscale) entities in a
restricted geometry by the controlled action of (laser) light,
and optical trapping nanometry is a method of making nanoscale
measurements of such entities. In this experiment, the optically
trapped entity is a fluorescent bead (1 micron diameter)
crosslinked with the biotin of the singlet microtubule, the
method allowing measurement of the nanoscale displacements of the
bead-microtubule entity as it is moved by the underlying doublet
dynein arms.
-------------------
Related Background:
DETAILS OF DYNEIN MOTOR DOMAIN MECHANISMS
... Gee et al (3 authors at 3 installations, US) report that the
entire carboxy-terminal two-thirds of the 532K dalton force-
producing heavy chain subunit of dynein is required for ATP-
binding activity. They have also identified a distal microtubule-
binding domain that apparently forms a hairpin-like stalk. The
authors suggest the mechanism for dynein force production differs
substantially from that of other motor proteins.
QY: Richard B. Vallee 
(Nature 11 Dec 97) (Science-Week 2 Jan 98)
[For more information: http://scienceweek.com/search/search.htm]


4. CELL BIOLOGY: ON THE SIGNIFICANCE OF INTRACELLULAR CIRCULATION
The prevailing idea in biology is that many physiological and
molecular functions are the sum of individual processes linked in
sequence, although when studied in isolation, many such
individual processes are without apparent function. How such
systems evolve and become regulated continues to be one of the
most important puzzles confronting both biochemists and cell
physiologists.
... ... P.W. Hochachka (University of British Columbia, CA)
presents a review of current theoretical approaches to cell
metabolism and regulation, the author making the following
points:
     1) Two views currently dominate research into cell function
and regulation: The first view (Model #1) assumes that cell
behavior is quite similar to that expected in a watery bag of
enzymes and ligands. The second view (Model #2) assumes that
3-dimensional order and structure constrain and determine
metabolite behavior.
     2) A major puzzle in the study of cell metabolism is that
essentially all metabolite concentrations are remarkably stable
(are *homeostatic) over large changes in pathway fluxes. The
author calls this the "stability paradox". For muscle cells, for
example, *adenosine triphosphate (ATP) and oxygen are the most
perfectly homeostatic, even though oxygen delivery and metabolic
rate correlate in a 1:1 fashion. In total, more than 60
metabolites are known to be remarkably homeostatic in differing
metabolic states.
     3) Several explanations of stability are usually given by
traditional Model #1 studies -- none of which apply to all
enzymes in a pathway, and all of which require diffusion as the
means for changing enzyme-substrate encounter rates. In contrast,
recent developments in our understanding of intracellular
*myosin, kinesin, and dynein motors running on *actin and tubulin
tracks or cables provide a mechanistic basis for regulated
intracellular circulation systems with *cytoplasmic streaming
rates varying over an approximate 80-fold range (from 1 to more
than 80 microns per second).
     4) These new studies suggest a Model #2 hypothesis of
intracellular perfusion or convection as a primary means for
bringing enzymes and substrates together under variable metabolic
conditions. In this view, changes in intracellular perfusion
rates causes changes in enzyme-substrate encounter rates and thus
changes in pathway fluxes -- with no requirement for large
simultaneous changes in substrate concentrations. The author
concludes: "The ease with which this hypothesis explains the
stability paradox is one of its most compelling features."
-----------
P.W. Hochachka: The metabolic implications of intracellular
circulation.
(Proc. Natl. Acad. Sci. US 26 Oct 99 96:12233)
QY: P.W. Hochachka [pwh@zoology.ubc.ca]
-----------
Text Notes:
... ... *homeostatic: 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.
... ... *adenosine triphosphate (ATP): ATP 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
various cell components.
... ... *myosin, kinesin, and dynein motors: It is now recognized
that the interiors of biological cells are structurally complex,
and that this structure is dynamic. Microtubules are part of the
cytoskeleton of biological cells, the quasi-rigid matrix that
among other things determines cell shape. The microtubules are 25
nanometers in diameter, and composed of the protein tubulin. They
occur in regular arrays in various cell organelles, and in the
cytoplasm in general, and they contribute not only to cell shape,
but also to cell motility. Microfilaments are 4 to 6 nanometers
in diameter, highly variable in length, and are found in all
eukaryotic cells. They are composed of a protein called "actin"
and several other accessory proteins, and they are important in
cell locomotion and in the molecular dynamics of muscle cells.
"Motor proteins" are mechanico-chemical enzymes involved in
locomotion or transport, and there are three families of such
proteins: kinesins, dyneins, and myosins. Kinesins and dyneins
are microtubule based motor proteins, while myosin is a
microfilament based motor protein. In general, as mechanico-
chemical enzymes, motor proteins convert energy from hydrolysis
of nucleotides to mechanical force, and since they are involved
in many important cellular events, the molecular details are
currently the focus of intensive research.
... ... *actin and tubulin tracks or cables: See previous note.
... ... *cytoplasmic streaming: Supremely evident to biologists
who study living cells with the light microscope is the fact that
the interiors of cells are often in visible motion, the
cytoplasmic contents circulating in various streams. The
classical name for these movements was "cytoplasmic streaming",
and for nearly a century, such movements remained a profound
puzzle in biology. With the advent of molecular biology,
intracellular streaming motion was recognized as a phenomenon
related to dynamic motor proteins.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 7Jan00
[For more information: http://scienceweek.com/search/search.htm]


5. NEUROBIOLOGY: ON THE STABILITY OF FAST-SYNAPSE RECEPTORS
In neurobiology, the term "axon" refers to the long extensions of
neurons that propagate electrical activity (action potentials) to
other cells, and the term "synapse" refers to a functional
junction between one neuron and another neuron or between a
neuron and another type of cell (e.g., a muscle cell). The
general paradigm is that electrical activity in neuron (A)
provokes a response in cell (B); the (A) side of the junction is
called "presynaptic" and the (B) side of the junction is called
"postsynaptic". In mammalian nervous systems, the major event at
nearly all synapses is the release of a neurotransmitter
substance by the presynaptic contact (the terminal of the axon of
the input neuron), the neurotransmitter interacting with specific
membrane molecular receptors associated with the postsynaptic
contact. At the nerve-muscle junctions (neuromuscular junctions)
in the "voluntary" fast-response muscle systems, the
neurotransmitter substance is usually acetylcholine, the
transmitter substance released into junctions of relatively
complicated micron-scale architecture ("muscle endplates"). In
general, in mammals, the system is one which has evolved to make
possible rapid activation of important fast-responding muscle
systems, with stringent controls over the range and dynamics of
excitation of these muscle systems by their input.
... ... Miriam M. Salpeter (Cornell University, US) presents a
commentary on some current research concerning "fast synapses",
the author making the following points:
     1) In synapses that must generate action potentials within
microseconds of neurotransmitter release (fast synapses), the
receptors need to be clustered in the postsynaptic membrane at
high density and close to where the neurotransmitter is released.
The neuromuscular junction has just such an organization. The
principal transmitter at the neuromuscular junction is
acetylcholine, which is released from the presynaptic nerve
terminal within 50 nanometers of the postsynaptic muscle membrane
that contains densely arrayed acetylcholine receptors --
approximately 10^(4) receptors per square micron.
     2) At such a junction, there is a steady turnover of
acetylcholine receptors, with newly synthesized receptors
replacing those that are periodically degraded and internalized
(i.e., withdrawn into the cell interior). Both the location on
the muscle membrane where the acetylcholine receptors are
internalized, as well as the regulatory mechanisms involved, have
not yet been determined.
     3) In recent experiments, Akaaboune et al (see below)
observed individual neuromuscular junctions and studied these
repeatedly over time. These experiments demonstrate that the
muscle membrane surrounding the neuromuscular junction
(perijunctional membrane) is involved in receptor turnover, and
that muscle contraction is essential for regulating acetylcholine
receptor degradation.
... ... In the same issue of the journal, Akaaboune et al
(Washington University St. Louis, US) report the following:
     1) Quantitative *fluorescence imaging was used to study the
regulation of acetylcholine receptor number and density at
neuromuscular junctions in living adult mice. At fully functional
synapses, these receptors have a half-life of approximately 14
days. However, 2 hours after neurotransmission was
pharmacologically blocked (by the agent bungarotoxin), the half-
life of these receptors was reduced to less than 1 day, with a
degradation rate 25 times faster than normal. Most of the lost
receptors were not quickly replaced. Direct muscle stimulation or
restoration of synaptic transmission inhibited this rapid
degradation process.
     2) Receptors removed by the degradation process from
nonfunctional synapses persisted for hours in the perijunctional
membrane before being locally internalized. Dispersed receptors
could also reaggregate at the junction once neurotransmission was
restored. The authors suggest that the rapid and reversible
alteration in neurotransmitter receptor density at the
neuromuscular junction in vivo may parallel changes believed to
occur in the central nervous system at synapses undergoing
*potentiation and *depression, and that this observed dependence
of neurotransmitter receptor density on activity in the
neuromuscular junction has important implications for clinical
aspects of diseases of such junctions.
-----------
Miriam M. Salpeter: The constant junction.
(Science 15 Oct 99 286:424)
QY: Miriam M. Salpeter [mms13@cornell.edu]
-----------
M. Akaaboune et al: Rapid and reversible effects of activity on
acetylcholine receptor density at the neuromuscular junction in
vivo.
(Science 15 Oct 99 286:503)
QY: Mohammed Akaaboune [mohammed@nmj.wustl.edu]
-----------
Text Notes:
... ... *fluorescence imaging: The technique in these experiments
involved the use of tetramethyl-rhodamine-labeled alpha-
bungarotoxin and the assay of localized fluorescence intensity
with time. The term "bungarotoxin" refers to a group of
neurotoxins derived from the venom of the krait snake Bungarus
multicinctus. Alpha-bungarotoxin is a single polypeptide chain of
74 amino acid residues, the molecule known to bind to muscle
endplate acetylcholine receptors and cause paralysis by
preventing synaptic activation. (The krait snake belongs to the
group Elapidae: cobras, mambas, kraits, coral snakes.)
... ... *potentiation: In this context, in general, an increase
in the effects of synaptic input.
... ... *depression: In this context, in general, a decrease in
the effects of synaptic input.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 7Jan00
[For more information: http://scienceweek.com/search/search.htm]


6. ANTHROPOLOGY: GENOMIC ANALYSIS OF HUMAN HISTORY
An important new trend in recent years has been a merging of the
research interests of molecular geneticists, anthropologists, and
historians. New tools of genomic analysis are beginning to shed
light on historical questions such as migrations of ancient
peoples, differences in migration patterns of males and females,
historical demography of cultures with ancient roots, patterns of
human genetic diversity, and so on. It is apparent that in
certain areas of the study of history, historical analysis is
undergoing a methodological transformation.
... ... K. Owens and M-C. King (University of Washington, US)
present a review of recent applications of genomic analysis to
history and anthropology, the authors making the following
points:
     1) Molecular genetics has begun to revolutionize the study
of human evolution. Analysis of human genomes now offers the
possibility of understanding movements and events of more recent
human history, and analysis of records written in human DNA can
complement historical analysis of records written by human
observers.
     2) Human migrations: Every present-day population retains
clues to its ancient roots, and common ancestries can be
confirmed and human migrations traced by comparing DNA
frequencies of present-day populations. Early migrations of
modern humans out of Africa have been traced by analysis of DNA
sequences; more recent human migrations have been followed
through genetic trails as well. An example is the application of
statistical analysis of classical *polymorphisms to the question
of ancient migrations within Europe. One important question
concerning migrations in general is whether males and females
migrate in the same ways. Genetic analysis of sequences of
*mitochondrial DNA (mtDNA) and *Y chromosome markers carried out
in the past few years suggest that the migration rates of males
and females have been dramatically different for much of human
history, with higher migration rates among females than among
males. When females relocate to the birthplaces of their spouses,
children are born close to the birthplaces of their fathers but
further from the birthplaces of their mothers. Most individual
females do not move far, but over hundreds of generations, the
genetic effects of their movements accumulate, leading to the
observed migration patterns.
     3) Genetic perspectives on cultural history: Genomic
analysis can reveal the historical demography of cultures with
ancient roots, and also indicate how current populations are
related to each other, including the extent and timing of their
contacts. An important historical question, for example, concerns
the movement of people and genes along ancient trade routes. The
Kazakh, Uighur, and Kirghiz populations of central Asia live
along the Silk Road, the trade route between Europe and Asia that
flourished between approximately 200 B.C. and 400 A.D. Analysis
of mitochondrial DNA sequences of these populations suggests that
they are descended from people moving from Europe to Asia and
vice versa more than 2000 years ago, albeit long after the early
human migrations out of Africa. Y chromosome variation in part
parallels language differences among these populations, whereas
mitochondrial DNA variation does not. Y chromosome data from
central Asia and from other regions of the world suggest that
genetic differences at linguistic boundaries are due primarily to
male rather than female isolation. Genetic evidence also supports
the oral tradition that the Lemba, who are now Bantu-speaking
people of southern Africa, derive from Jews who migrated from the
Middle East to Yemen 2700 years ago, and from Yemen to southern
Africa 2400 to 2000 years ago. More than 50 percent of Lemba Y
chromosomes carry *haplotypes that are common among Jewish
populations but absent in their African neighbors.
     5) Genetics, history, and race: Of importance is the fact
that genetic differences of populations from different continents
represent only approximately 10 percent of human genetic
diversity: no major genetic discontinuities across populations
have been observed. Most human genetic variation antedates the
migration of modern humans out of Africa. The possibility that
human history has been characterized by relatively homogeneous
genetic groups ("races"), distinguished by major biological
differences, is not consistent with genetic evidence. Variation
in traits, including skin color, popularly used to identify
"races", is likely due to straightforward mechanisms involving
limited numbers of genes with very specific physiological
effects. Of course prejudice does not require a rational basis,
let alone an evolutionary one, but the myth of major genetic
differences across "races" is nonetheless worth dismissing with
genetic evidence.
-----------
K. Owens and M-C. King: Genomic views of human history.
(Science 15 Oct 99 286:451)
QY: Kelly Owens, Univ. of Washington Seattle 206-543-8992.
-----------
Text Notes:
... ... *polymorphisms: A genetic polymorphism is a naturally
occurring variation in the normal nucleotide sequence of the
genome within individuals in a population. Variations are denoted
as polymorphisms only if they cannot be accounted for by
recurrent mutation and occur with a frequency of at least about 1
percent.
... ... *mitochondrial DNA (mtDNA): Mitochondria are
double-membrane enclosed organelles of cells that are involved
with several important biochemical pathways, including electron
transport and oxidative metabolism. Various types of eukaryotic
cells (i.e., cells containing membrane-bound organelles) may
contain from a few to several thousand mitochondria in each cell
type. The mitochondria are relatively large cylindrical
structures up to 10 microns long and up to 2 microns in diameter,
and they are believed to have originated as organisms that became
symbiotic with eukaryotic cells. Mitochondrial DNA is believed to
evolve in parallel with nuclear DNA, but since sperm
mitochondria are apparently quickly destroyed inside egg cells,
mitochondrial DNA is primarily inherited only in the maternal
lineage in animals.
... ... *Y chromosome markers: The Y chromosome is one of the two
chromosomes that determine sex in many animals, including humans,
and it carries mostly male-specific genes.
... ... *haplotypes: (haploid genotypes) The term "haplotype"
refers to a particular combination of genes (specifically,
*alleles) in a defined region of a chromosome.
... ... *alleles: (allelomorph) An "allele" is one of two or more
forms of a given gene that control a particular characteristic,
with the alternative forms occupying corresponding loci on
homologous chromosomes. Different alleles usually produce
different characteristics in an organism, e.g., brown versus blue
eyes.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 7Jan00
[For more information: http://scienceweek.com/search/search.htm]
-------------------
Related Background:
PALEOLITHIC HUMAN POPULATION EXPANSION IN AFRICA
Human populations have undergone dramatic expansions in size, but
other than the growth associated with agriculture, the dates and
magnitudes of those expansions have never been resolved. Genetic
approaches to the study of human population expansions have
focused on variation at a single genetic locus, the "control
region" of *mitochondrial DNA. But in the study of demographic
history, single-locus investigations suffer from pronounced
statistical and biological limitations. The statistical problem
is that the conclusions rely on only one particular realization
of a gene genealogy, the "tree" determining the ancestral
relationships among a set of *alleles. The biological problem is
that there are a large number of functional genes in the
mitochondrion, and due to a complete linkage, a selective sweep
for any one of the genes may lead to a spurious signal of
expansion. ... ... Reich and Goldstein (University of Oxford, UK)
present two new statistical tests for population expansion, using
variation at a number of unlinked genetic markers to study the
demographic histories of natural populations. The authors report
that analysis of genetic variation in various aboriginal
populations throughout the world reveals highly significant
evidence for a major human population expansion in Africa, but no
evidence of expansion outside of Africa. The inferred African
expansion is estimated to have occurred between 49,000 and
640,000 years ago, certainly before the Neolithic expansions, and
probably before the splitting of African and non-African
populations. The authors suggest that in showing a significant
difference between African and non-African populations, their
analysis supports the unique role of Africa in human evolutionary
history. The authors also suggest that the missing signal in non-
African populations may be the result of a population bottleneck
associated with the emergence of these populations from Africa,
as postulated in the "Out of Africa" model of modern human
origins.
QY: David B. Goldstein 
(Proc. Natl. Acad. Sci. US 7 Jul 98 95:8119)
(Science-Week 7 Aug 98)
-------------------
Text Notes:
... ... *mitochondrial DNA: See notes to previous report.
... ... *alleles: See notes to previous report
-------------------
Related Background:
GENETIC TRACES OF ANCIENT DEMOGRAPHY
The term "haploid loci" refers to genome locations that derive
from only one parent... A "nonrecombining" part of a genome is a
part that does not vary when the entire genome is replicated
during reproduction. The Pleistocene is the geological time
period from about 2 million years ago to about the end of the
last glaciation about 10,000 years ago. Modern man is believed
to have evolved during the Pleistocene.
... ... Harpending et al (6 authors at 3 installations, US), in a
study of the demographic history of the human species as revealed
by patterns of gene differences, report that haploid loci like
mitochondrial DNA and the nonrecombining part of the Y chromosome
show a pattern indicating expansion from a population of only
several thousand during the late middle or early upper
Pleistocene. The authors suggest our ancestral population size
during nearly the whole Pleistocene was of the order of 10,000
breeding individuals, and that genetic evidence denies any
version of the multiregional model of modern human origins, and
implies instead that our ancestors were effectively a separate
species for most of the Pleistocene, a small population probably
occupying an area the size of Swaziland or Rhode Island rather
than a whole continent. The authors further suggest that
archeologists should find and identify this population.
QY: Henry C. Harpending [harpend@ibm.net]
(Proc. Natl. Acad. Sci. US 17 Feb 98) (Science-Week 20 Mar 98)
-------------------
Related Background:
Y CHROMOSOME EVIDENCE INDICATES AFRICAN ORIGINS OF MAN
The Y chromosome is one of the two chromosomes that determine sex
in many animals, including humans, and it carries mostly male-
specific genes. Genetic polymorphisms are individual functional
variations of specific genes or genetic markers that occur in a
population with a significant frequency, e.g., more than 1%.
... ... At a recent symposium on human evolution (Cold Spring
Harbor Laboratory, NY US), a consensus was apparently reached
that current studies of human Y chromosome polymorphisms indicate
that the major human migrations that occurred had their source in
Africa, and that a small number of present African populations,
the Ethiopians, Sudanese, and south African Khoisans, possess
markers that have been conserved since that time. The data are
considered to confirm the recent mitochondrial DNA studies which
also indicate Africa as the source of human migrations. Some
paleoanthropologists are calling the Y chromosome results an
"unquestionable major breakthrough".
(Science 31 Oct 97) (Science-Week 21 Nov 97)
[For more information: http://scienceweek.com/search/search.htm]


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

Correction:

In the Focus Report of 31 Dec 99, the line near the end:

"knowing how to reach plans are represented in the brain..."

should read:

"knowing how reach plans are represented in the brain..."

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

IN FOCUS: NEUTRINOS AND OBSERVATIONAL ASTRONOMY
     "The invention of the optical telescope 400 years ago
fundamentally changed our view of the Cosmos around us, as well
as our view of ourselves in that Cosmos. The enhanced photon-
detection efficiency of the telescope, compared with the naked
eye, revolutionized observational astronomy. One hundred years
after burning Giordano Bruno at the stake, the Vatican, under the
weight of an avalanche of experimental information obtained with
optical telescopes, officially recognized heliocentrism as
Catholic canon. Within the last 40 years, however, the
limitations of the optical telescope have become increasingly
apparent. Detection of photons as tracers of astrophysical
processes have two primary shortfalls: 1) they are sensitive only
to those astrophysical processes that specifically produce
visible light (an extremely small portion of the entire
electromagnetic frequency range), and 2) because the interstellar
medium is not empty, and is rather a soup of dust (1 proton per
cubic meter on average), low-energy microwave photons left over
from the Big Bang ([at] 400 per cubic centimeter), infrared
starlight, etc., the likelihood of an optical photon penetrating
the interstellar medium from the edge of the Cosmos and reaching
our terrestrial telescopes without being perturbed, absorbed, or
deflected en route, decreases with both the energy of the photon
and the distance from Earth to source point. This motivates the
search for alternative means of collecting astronomical
information.
     "Neutrinos are 'fundamental' particles in the sense that,
like quarks or electrons, they are believed to have no
constituents. This is contrasted with protons, for example, which
are believed to contain three smaller quarks. Neutrinos are also
the most inert of the presently known fundamental particles;
because they have no electric charge, they do not participate in
either electric or magnetic interactions; unlike quarks, they do
not participate in the 'strong nuclear force' that holds the
proton together and is responsible for the awesome explosive
force of the hydrogen bomb. Neutrinos interact only by means of
the 'weak' interactions, which are, indeed, quite weak. A typical
neutrino produced in the interior of the Sun will travel
unscathed through a light-year of lead before interacting. This
represents a unique experimental opportunity -- neutrinos from
the Sun carry direct information about the solar interior.
Alternatively, neutrinos from the edge of the Universe will
easily penetrate the interstellar medium without being absorbed
or deflected. However, the inertness of the neutrino immediately 
presents an experimental challenge: one must use an extremely
large volume of material to detect the very rare neutrino
interactions."
-----------
D. Besson et al: Neutrinos
(Proc. Natl. Acad. Sci. US 7 Dec 99 96:14201)


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