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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.
June 16, 2000 -- Vol. 4 Number 24
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Here is a biologist examining a culture of
nerve cells in a small dish. One set of nerve
cells examining another set of nerve cells.
Not quite a trivial scenario.
-- Anonymous
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Contents of this Issue:
1. Astrophysics:
Dwarf Galaxies and Starbursts
-----------------------------
Dwarf starburst galaxies are of great interest to astronomers
because they make possible the study of phenomena that cannot be
observed anywhere else. (Includes related background material.)
2. Astrophysics:
The Physics of the Sun and Terrestrial Climate
----------------------------------------------
It appears that the global warming since 1950 is in part a
consequence of the continuing increase in solar brightness,
seriously aggravated by the extravagant burning of fossil fuel.
(Includes related background material.)
3. Geophysics:
Tidal Cycles and Rapid Climate Change
-------------------------------------
A proposal that sudden climate changes on the scale of thousands
of years are produced in part by variations of global oceanic
tide-raising forces related to periodic motions of the Earth and
Moon. (Includes related background material.)
4. History of Biology:
On Drosophila and Genome Research
---------------------------------
The fruit fly Drosophila melanogaster one of the most important
biological systems in the history of biology, a laboratory
organism involved in pioneering studies of genetic mapping, whole
genome mutational screens, and functional alteration of the
genome by gene transfer. (Includes related background material.)
5. Molecular Biology:
On Biomolecules and Nanotechnology
----------------------------------
Many of the engineering problems in nanotechnology have already
been solved by biological systems as a consequence of 3 billion
years of evolution. (Includes related background material.)
6. Medical Biology:
Mitochondria in Human Disease
-----------------------------
In addition to their well-established role in providing ATP to
drive energy-requiring processes within biological cells,
mitochondria play a central role in apoptosis, the process of
programmed cell death, and mitochondrial dysfunctions are now
recognized as important components of a number of diseases.
(Includes related background material.)
7. In Brief: Of Genes and Money
8. In Focus: Energy and the Death of Living Systems
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
1. ASTROPHYSICS:
DWARF GALAXIES AND STARBURSTS
In general, a "starburst galaxy" is a galaxy whose energy
output is dominated by radiation from recently formed stars. The
activity is transient, since the rate of star formation in such a
galaxy is much greater than could be sustained for the whole life
of the galaxy. Radiation from a starburst galaxy is emitted
mainly in the ultraviolet region from hot young massive stars,
but this radiation is absorbed and re-emitted by dust in
interstellar space to give very high luminosities at far infrared
wavelengths. Many starburst galaxies have been discovered by the
Infrared Astronomical Satellite (IRAS), and some of these
galaxies are the most luminous galaxies known, radiating at
10^(14) solar-luminosities in the infrared.
A "dwarf galaxy" is ordinarily a small low-luminosity
galaxy. There are no dwarf spiral galaxies known. In recent
years, dwarf starburst galaxies have been of great interest to
astronomers because they make possible the study of phenomena
that cannot be observed anywhere else.
... ... Sara C. Beck (Tel Aviv University, IL) presents a review
of dwarf starburst galaxies, the author making the following
points:
1) Astronomers have recently discovered that dwarf galaxies
are far more common than previously believed. In addition, these
galaxies are quite different from larger galaxies: they pass
billions of years in a dormant state, and then they erupt in
furious and short-lived bursts of star formation ("starbursts").
Starbursts also occur in larger galaxies, but the radiation from
larger galaxies is usually obscured by other galactic emissions.
Only in dwarf starburst galaxies is it possible to obtain a clear
look at the starburst phenomenon. Dwarf galaxies also hold clues
to the early history of the Universe: they are relics composed of
material that has changed little since the Big Bang.
2) Ordinary star formation in our Galaxy is a slow steady
process involving the contraction of vast clouds of interstellar
gas and dust, with approximately 1 solar-mass of gas and dust
turned into a new star each year. In contrast, a starburst during
a relatively brief period (from 1 million to 20 million years) in
which the rate of star formation is much higher than average
(e.g., 100 times higher than the rate of star formation in our
Galaxy).
3) In a starburst galaxy, the sudden high star formation
rate causes a dramatic rise in the brightness of the galaxy.
Because starbursts are relatively brief, they are dominated by
the radiation from hot young stars of 20 solar-masses or more,
stars which have lifetimes of only a few million years. Such
stars are tens of thousands of times brighter than the Sun, and
they heat and ionize the dense clouds of gas and dust from which
they form. The clouds absorb the visible and ultraviolet light of
the stars and then reradiate the energy as radio and infrared
emissions. A strong starburst can be almost as bright as a
*quasar, which is the most luminous object in the Universe.
Because the luminosity of a starburst is concentrated in the
radio and infrared parts of the spectrum, the starburst
phenomenon has been studied only in the past 20 years as new
telescopes and satellites have made possible observations at
these wavelengths.
4) Dwarf galaxies are not merely scaled-down versions of
large galaxies: the evolution of dwarf galaxies is driven by
different mechanisms. The large spiral galaxies contain giant
clouds of molecular hydrogen, helium, and dust that can readily
form stars. The spiral-arm pattern is maintained by density waves
that trigger star formation by compressing the molecular clouds
as the density waves pass through them. As a result, spiral
galaxies are never completely quiescent and always contain some
new stars. In contrast, dwarf galaxies have little molecular
hydrogen and a great deal of atomic hydrogen. In a typical dwarf
galaxy, the mass contained in the clouds of atomic hydrogen is 10
times greater than the mass of the stars in the galaxy. Because
these clouds are not as dense as clouds of molecular hydrogen,
they are less likely to undergo gravitational collapse and
produce stars. Furthermore, dwarf galaxies do not have density
waves or other organized gas motions that can cause a cloud to
collapse. Thus, dwarf galaxies pass the majority of their
existence in a quiescent state, a phase during which all their
stars are faint, red, and old. Only the starburst dwarf galaxies
contain the hot bright blue stars that indicate recent star
formation.
5) The apparently random distribution of starburst clumps in
dwarf galaxies raises the question of how star formation can
spread through a galaxy that has no spiral arms or other
organized gas motions. The current consensus model is called
"self-propagating stochastic star formation". In this model, a
starburst clump in one part of a galaxy triggers secondary
starbursts in other parts. The massive young stars in the first
center of activity disturb the gas in an adjacent region with
stellar winds, ionization, and other energetic activities. The
disturbed gas then collapses and begins its own burst of star
formation, and the process continues until there is not enough
gas in position to be affected by the young stars. This model is
apparently suited to the progress of star formation in dwarf
galaxies, but the model is probably not applicable to spiral
galaxies. The model also leaves open the question of what causes
the initial starburst.
-----------
Sara C. Beck: Dwarf Galaxies and Starbursts.
(Scientific American June 2000)
QY: Sara C. Beck, Tel Aviv University, Tel Aviv, IL.
-----------
Text Notes:
... ... *quasar: (quasi-stellar object). An extremely luminous
source radiating energy over the entire spectrum from x-rays to
radio waves. Quasars are apparently the oldest and most distant
objects in the universe.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 16Jun00
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
A CLUSTER OF MASSIVE STARS NEAR OUR GALACTIC CENTER
The relative number of newborn stars of different masses in a
galaxy (the "*initial mass function") determines whether the
galaxy's interstellar gas condenses mainly into long-lived low-
mass stars, as in the disk of normal spiral galaxies, or into
short-lived massive stars, as has been proposed for "*starburst
galaxies". The center of our own Galaxy is not a full-fledged
starburst region, but its star-formation rate per unit volume of
space is nevertheless approximately 1000 times that of the disk.
It is usually extremely difficult to study the initial mass
function near the center of the Galaxy, because the dust in the
gas clouds obscures the starlight, and the relatively rare young
stars are mixed with much more numerous older stars. ... ...
Serabyn et al (3 authors at 2 installations, US) now report high-
resolution infrared observations of a compact cluster of stars in
the central region of our Galaxy, the observations revealing
approximately 100 young massive *main-sequence stars, several of
which seem to be among the most massive in the Galaxy. The
authors suggest this cluster may be a weak analogue of the large
star clusters in starburst galaxies, and that this opens the
possibility of studying the starburst phenomenon by means of a
local example.
QY: E. Serabyn
(Nature 30 Jul 98)
-------------------
Related Background:
... ... *initial mass function: In what is known as the "Salpeter
mass function", the number of stars of a given mass in a unit
volume of space is proportional to the mass to the (-2.35) power.
But after birth, the masses of stars change as a result of mass
loss and mass transfer, and the Salpeter mass function holds
strictly only for stars at the instant of birth. Under this
constraint, the Salpeter mass function is called the "initial
mass function".
... ... *starburst galaxies: A starburst galaxy is a galaxy in
which a massive burst of star formation is taking place, and such
galaxies are characterized by high infrared luminosities.
... ... *main-sequence stars: The Hertzsprung-Russell diagram is
a plot of stellar absolute magnitude against spectral type, and
is one of the most useful diagrammatic aids in astrophysics. The
Main Sequence is a region on the Hertzsprung-Russell diagram
where most stars, including our own Sun, are situated. The course
of a star's evolution can be traced as a particular path in the
H-R diagram, with the paths of various types of stars showing
significant differences.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 21Aug98
For more information: http://scienceweek.com/swfr.htm
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2. ASTROPHYSICS:
THE PHYSICS OF THE SUN AND TERRESTRIAL CLIMATE
The Sun, a *main-sequence star 1.4 million kilometers in
diameter, is composed predominantly of hydrogen and helium
(approximately 70 percent hydrogen by mass, 28 percent helium by
mass, and 2 percent heavier elements by mass) and it generates
its energy via nuclear fusion processes, particularly via the
*proton-proton chain reaction. As a result, the Sun is losing
mass at a rate of approximately 4 million metric tons per second.
The generation of energy occurs in the "central core", which
has a temperature of approximately 15 million degrees kelvin, is
approximately 400,000 kilometers in diameter, and contains
approximately 60 percent of the mass of the Sun in 2 percent of
its volume.
Outside the core is the "radiative zone", an envelope of
unevolved material through which energy from the core is
diffusively transported by successive absorption and emission of
radiation in collisions between atomic particles. It has been
estimated that it may take from 1 million years to as long as 10
to 20 million years for the energy generated in the core to reach
the surface.
The radiative zone extends to within 200,000 kilometers of
the surface. In the surface layer (the "convective zone"), where
the temperature is only 1 million degrees kelvin, convection is
the most important mode of energy transport.
... ... Eugene N. Parker (University of Chicago, US) presents a
review of the physics of the Sun, the author making the following
points:
1) The Sun is essentially a thermonuclear core enclosed in
an opaque shroud that insulates the high temperature of the core
from the cold Universe outside. The core is brighter than 10
supernovas at maximum light, but the enclosing shroud turns back
all but one part in 2 x 10^(11) of the thermal radiation. The
outward journey of the energy from the core takes approximately 1
million years, which illustrates the immense opacity and thermal
capacity of the shroud.
2) Approximately 10^(-5) of the outflowing energy from the
core of the Sun is diverted into magnetic fields that produce a
variety of exotic effects, including *coronal mass ejection,
*solar flares, the million degree corona, the *solar wind, and x-
ray emission. These phenomena are of interest to the physicist
because they represent unanticipated manifestations of classical
physics, extrapolations to astronomical scales of basic
principles traditionally studied in terrestrial laboratories.
3) The total luminosity of the Sun varies with time, and
systematic monitoring of several Sun-type stars during the past 4
decades reveals magnetic activity cycles comparable to that of
the Sun. The luminosities of some of those stars have been
monitored for approximately 15 years, and the data show
approximately the same variation as the magnetic activity.
4) The Earth contains a great deal of information about past
solar activity. The rate of production of carbon-14 depends
directly on the intensity of *cosmic rays, and such rays are
partially excluded from the Solar System by the outward sweep of
magnetic fields in the solar wind. Thus the cosmic ray intensity
and carbon-14 production vary oppositely to the general level of
solar activity.
5) The carbon-14 record indicates that over the last 70
centuries the Sun has been without normal activity for 10
centuries and hyperactive for 8 centuries. The other 52 centuries
were variable but more or less normal. The most recent quiescent
period was from 1645 to 1715, the period called the "Maunder
Minimum". The 12th century "Medieval Maximum" is the most recent
epoch of hyperactivity. The empirical relation between the total
luminosity and magnetic activity, based on many Sun-type stars,
suggests that the Sun was fainter during the *Maunder Minimum by
0.4 +- 0.2 percent, and perhaps brighter by a comparable amount
during the Medieval Maximum. The mean annual temperature in the
northern temperate zone was lower than normal by 1 to 2 degrees
centigrade during the Maunder Minimum and higher by 1 to 2
degrees centigrade during the Medieval Maximum. The fractional
change in temperature is comparable to the fractional change in
solar brightness, with the implication that the Sun is the driver
of the climate. The consequences for agriculture were severe
during both periods, the Maunder Minimum being disastrous in
northern Europe and China, and the Medieval Maximum disastrous in
the semi-arid regions. These periods of abnormal activity of the
Sun are without explanation, as are the variations within the so-
called "normal centuries".
6) The general level of solar activity doubled or tripled
from 1900 to 1950, an estimate based on sunspot numbers and on
the intensity of geomagnetic activity. This increase suggests an
increase in solar luminosity by perhaps one part in 2000, and the
author suggests it is interesting to note that the mean
temperature in the northern temperate zone, as well as the
surface sea water temperatures, rose during the same period.
"Warmer seas, of course, reduce the rate at which atmospheric
carbon dioxide is absorbed into the oceans. It appears that the
global warming since 1950 is in part a consequence of the
continuing increase in solar brightness, seriously aggravated by
the extravagant burning of fossil fuel. So the mystery of the
variations in the total luminosity of the Sun is part of the
complicated picture of global warming."
[Editor's note: See report #3 in this issue for another approach
to millennial-scale climate changes.]
-----------
Eugene N. Parker: The physics of the Sun and the gateway to the
stars.
(Physics Today June 2000)
QY: Eugene N. Parker, University of Chicago 312-702-9808.
-----------
Text Notes:
... ... *main-sequence star: The Main Sequence is a region on the
*Hertzsprung-Russell diagram where most stars lie, including our
own Sun. The evolution of a star can be diagrammed as a movement
along the Main Sequence and an eventual branching off the Main
Sequence to regions associated with various types of old stars.
... ... *Hertzsprung-Russell diagram: The Hertzsprung-Russell
diagram is a plot of stellar absolute magnitude against spectral
type, and is perhaps the most useful diagrammatic aid in
astrophysics. It allows the portrayal of the evolution of a star
as occurring along various paths in the diagram.
... ... *proton-proton chain reaction: A chain of nuclear
reactions inside a star that converts hydrogen to helium, with
the associated release of energy. In the reaction, 4 hydrogen
nuclei (protons) fuse to form one nucleus of helium, with the
production of a number of intermediate nuclei such as deuterium
and isotopes of lithium, beryllium, and boron. The proton-proton
reaction is the most important stellar reaction at temperatures
below 18 million degrees kelvin, and thus operates chiefly in
stars of less than 2 solar masses.
... ... *coronal mass ejection: The corona is the Sun's faint
outer atmosphere, where the temperature is 2 million degrees
kelvin or more, the corona consisting of a low-density hot gas
that glows with a pale white color.
... ... *solar flares: A solar flare is a sudden release of
energy in the corona of the Sun, the phenomenon usually lasting
up to several hours (in rare cases, up to more than a day).
... ... *solar wind: The solar wind is the steady flow of charged
particles, consisting primarily of protons and electrons, from
the solar corona into interplanetary space. The solar-wind
particles have energies high enough to enable the particles to
escape the Sun's gravitational field, but the wind is influenced
by the Sun's magnetic field, and the particles can be trapped by
planetary magnetic fields.
... ... *cosmic rays: Highly energetic particles moving at close
to the speed of light and continuously bombarding the Earth's
atmosphere from all directions. The energies of the particles are
enormous and range from 10^(8) to over 10^(19) electronvolts.
... ... *Maunder Minimum: Named after the astronomer Edward W.
Maunder (1851-1928), who first noted the absence of reports of
sunspots in the period 1645 to 1715.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 16Jun00
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
HELIOSEISMOLOGY: PROBING THE INTERIOR OF THE SUN
... The science of helioseismology is the study of the solar
interior using observations of solar surface manifestations of
resonant sound waves (pressure modes; p-modes) traveling in the
solar interior. In other words, helioseismology is the study of
the solar interior structure by using the oscillations of its
surface. Since p-mode frequencies are *Doppler-shifted by motions
in the line of sight, they can also be used to study the internal
dynamics of the Sun, such as internal rotation and convection.
... ... P. Demarque and D.B. Guenther (2 installations, US CA)
present a review of current research in helioseismology, the
authors making the following points:
1) In 1962, Leighton et al discovered patches of the surface
of the Sun moving up and down with a velocity of the order of 15
centimeters per second, with periods of approximately 5 minutes.
Called the "5-minute oscillation", the motions were originally
believed to be local in character and somehow related to
turbulent convection in the solar atmosphere. In 1970, Ulrich
suggested that the phenomenon is global and that the observed
oscillations are the manifestation at the solar surface of
resonant sound waves (pressure modes or "p-modes") traveling in
the solar interior.
2) Stellar oscillation theory, the main theoretical
framework for helioseismology, also predicts the existence of
buoyancy driven modes (gravity modes, or "g-modes") that have
been observed in other astrophysical contexts, but it is not
clear at present whether g-modes are excited in the Sun. G-modes
are expected to be exponentially damped in convective regions, so
their amplitudes at the top of the solar convective envelope are
expected to be much smaller than in the radiative core. In
contrast to p-modes, which have maximum amplitudes in the outer
parts of the Sun, g-modes exhibit their largest amplitudes in the
solar core. If observable, g-modes would be sensitive probes of
the solar core, where p-modes are least sensitive.
3) There are many facets of helioseismology, and the field
has contributed to the study of stellar evolution and to
astrophysics and physics in general. The interpretation of a
wealth of ground-based data, most recently provided by the Global
Oscillation Network Group (GONG) project, a network of observing
stations distributed around the globe to observe the Sun
continuously, and the Solar and Heliospheric Observatory (SOHO)
space mission, have led to many advances. The most important
accomplishments of helioseismology include the following:
... ... a) The testing of the physical assumptions of stellar
evolution theory.
... ... b) The determination of the depth of the solar convection
zone.
... ... c) The reconstruction of the internal rotation profile in
the outer half of the solar radius.
... ... d) The detailed probing of the *superadiabatic transition
layer near the solar surface.
... ... e) The realization of the important role played by the
diffusion of helium in the interior of the Sun and the seismic
determination of the helium abundance in the convection zone.
... ... f) The determination of the age of the Sun by seismic
means.
... ... g) The setting of a strong constraint on *varying-
gravitational-constant cosmologies.
... ... h) The demonstration that the *solar neutrino discrepancy
is likely to reveal fundamental new knowledge about neutrinos and
their interaction with matter.
-----------
P. Demarque and D.B. Guenther: Helioseismology: Probing the
interior of a star.
(Proc. Natl. Acad. Sci. US 11 May 99 96:5356)
QY: P. Demarque, Yale University, 203-432-4771.
-----------
Text Notes:
... ... *main-sequence star: See main report.
... ... *proton-proton chain reaction: See main report.
... ... *Doppler-shifted: In general, the term "Doppler shift"
refers to the change in wavelength of electromagnetic radiation
as a result of relative movement between the source and the
observer.
... ... *superadiabatic transition layer: An adiabatic process is
any thermodynamic process, reversible or irreversible, that takes
place in a system without exchange of heat with the surroundings
of the system. All real processes are nonadiabatic in the sense
that some heat exchange always occurs. But close approximation to
an adiabatic ideal can be realized in practice. In the context of
this report, the "superadiabatic transition layer" is the
transition between deep convection, where the temperature
gradient is nearly adiabatic, and the shallow outer layers of the
Sun, where radiative losses dominate.
... ... *varying-gravitational-constant cosmologies: In general,
this term refers to cosmological theories dependent on a time-
varying universal gravitational constant. Recent
helioseismological data have provided a strong limit on the
variation of the universal gravitational constant during the
lifetime of the Sun, and this limit is stronger by almost one
order of magnitude than previous constraints.
... ... *solar neutrino discrepancy: Neutrinos are fundamental
particles with zero charge, possibly zero mass, and an angular
momentum factor (spin) of 1/2. Various processes produce
neutrinos: stellar nuclear reactions, reactions occurring during
supernova explosions, cosmic ray collisions with matter, etc.
Measurements of solar neutrinos have produced a mystery: the
neutrino density measured by detectors is approximately one-third
that expected from theoretical calculations of solar neutrino
emission. Two kinds of solutions have been proposed to resolve
this mystery, one solution involving revisions to the theory of
stellar structure, and the other solution involving revisions to
nuclear particle theory.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 30Jul99
For more information: http://scienceweek.com/swfr.htm
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
3. GEOPHYSICS:
TIDAL CYCLES AND RAPID CLIMATE CHANGE
Over the course of geologic history, the environment on
Earth has been far from static. Geologic evidence suggests that
600 million years ago the atmosphere lacked sufficient oxygen to
support animal life. More recently, as indicated by sediments
recording conditions over the past 500,000 years, the climate of
the planet varied between at least two different states. The
record from the past 150,000 years is particularly well-
preserved, offering details concerning repeated climate changes.
Between approximately 131,000 and 114,000 years ago, a warm
period similar to the climate of today occurred. This was
followed by what is called the "Wisconsin ice age", which ended
approximately 12,000 years ago when the current relatively warm
*Holocene period began.
Records of changes in Earth's climate are particularly clear
in high-resolution ice cores, which can preserve histories of
local climate (as reflected in snowfall and temperature),
regional climate (as reflected in wind-blown dust, sea salt,
etc.), and broader climate (as reflected in trace gases deposited
from the atmosphere) -- all on a common time scale that can
demonstrate synchrony of climate changes over wide regions.
High resolution ice-core and deep-sea sediment-core records
over the past million years show evidence of abrupt changes in
climate superimposed on slow alternations of ice-ages and
interglacial warm periods.
The term "solar irradiance" refers to the amount of solar
irradiation received from the Sun, and this can vary considerably
and with a complex of periodicities. In 1920, the meteorologist
Milutin Milankovic (1879-1958) proposed that small changes in
Earth's orbit, *precession, and *inclination affect the heat
balance and modify climate (the alterations called "solar
forcing"). The Milankovic hypothesis was not taken seriously
until 1976, when teams studying sediment cores from the ocean
floor constructed a history of ocean temperature that matched the
predictions of the Milankovic hypothesis, with two different
ocean cores providing similar results.
... ... C.D. Keeling and T.P. Whorf (University of California San
Diego, US) present a proposal to explain sudden climate changes
on the scale of thousands of years, the authors making the
following points:
1) Variations in solar irradiance are generally believed to
explain climatic change on 20,000- to 100,000-year time-scales in
accordance with the Milankovic theory of the ice ages, but there
is no conclusive evidence that variable solar irradiance can be
the cause of abrupt fluctuations of climate on time-scales as
short as 1000 years.
2) The authors propose that such abrupt millennial changes,
seen in ice and sedimentary core records, were produced in part
by well characterized almost periodic variations in the strength
of the global oceanic tide-raising forces caused by resonances in
the periodic motions of the Earth and Moon. A well-defined 1800-
year tidal cycle is associated with gradually shifting lunar
declination from one episode of maximum tidal forcing on the
centennial time-scale to the next. An amplitude modulation of
this cycle occurs with an average period of approximately 5000
years, associated with gradually shifting separation intervals
between *perihelion and *syzygy at maxima of the 1800 year cycle.
3) The authors propose that strong tidal forcing causes
cooling at the sea surface by increasing vertical mixing in the
oceans. The authors suggest that on the millennial time-scale,
this tidal hypothesis is supported by findings, from sedimentary
records of *ice-rafting debris, that ocean waters cooled close to
the times predicted for strong tidal forcing.
-----------
C.D. Keeling and T.P. Whorf: The 1800-year oceanic tidal cycle: A
possible cause of rapid climate change.
(Proc. Natl. Acad. Sci. US 11 Apr 00 97:3814)
QY: Charles D. Keeling [cdkeeling@ucsd.edu]
-----------
Text Notes:
... ... *Holocene period: The most recent epoch of the geologic
time scale, from approximately 10,000 years ago to the present.
... ... *precession: In general, the wobbling motion of a
spinning top or gyroscope in which the axis of rotation gradually
sweeps out a conical volume. The spinning Earth undergoes a slow
precession due to the combined gravitational attraction of the
Sun, Moon, and planets.
... ... *inclination: In general, the angle between the orbital
plane of a body and the reference plane centered on the object
around which the body is revolving.
... ... *perihelion: The point in an elliptical orbit around the
Sun which is nearest the center of the Sun.
... ... *syzygy: In this context, those points in the orbit of
the Moon where the Moon, Earth, and Sun are in a straight line.
... ... *ice-rafting debris: In general, in this context, "ice-
rafting" is the transport of rock particles and other materials
by floating ice.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 16Jun00
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
EARTH SCIENCES:
ICE-CORE EVIDENCE OF ABRUPT CLIMATE CHANGES
... Richard B. Alley (Pennsylvania State University, US)
reviews current ice-core research, the author making the
following points:
1) Dating and accumulation: On some glaciers and ice sheets,
sufficient snow falls each year to form recognizable annual
layers that are marked by seasonal variations in physical,
chemical, electrical, and isotopic properties. These variations
can be counted to determine ages of the layers, and accuracy of
the determination can be assessed by a number of ways, including
comparison to the chemically identified fallout of historically
dated volcanoes.
2) Paleothermometry: Ice cores are essentially local
paleothermometers. The classic paleothermometer is the stable
isotopic composition of water in the ice core. Natural waters
typically contain a fraction of 1 percent of isotopically heavy
water molecules, and the vapor pressure of this heavy water is
less than ordinary or "light" water. The result is that as an air
mass is cooled and precipitates, it preferentially loses heavy
water and must increasingly precipitate light water. Both
empirically and theoretically, isotopic composition of
precipitation and site temperature are strongly correlated in
time and space.
3) Aerosols: Anything in the atmosphere can eventually end
up in an ice core. Some materials are reversibly deposited, but
most materials remain in the ice unchanged. Although details of
the air-snow transfer process are complex and not yet completely
elucidated, large changes in concentrations of most materials in
ice can with confidence be said to reflect changes in the
atmospheric loading of these materials.
4) Gases: Trapped gases in ice-core bubbles are highly
reliable records of atmospheric composition, as indicated by
comparisons among cores from different ice sheets, and comparison
with instrumental records and the air in the *firn above the
bubble-trapping depth. The slight differences between bubble and
air composition caused by gravitational and thermal effects are
well understood and recognizable.
5) Geographic coverage: The ice-core record of abrupt
climate changes is clearest in Greenland. Although no other
record is available that spans the same time interval with
equally high time resolution, it appears that ice cores from the
Canadian arctic islands, high mountains in South America, and
Antarctica also contain indications of the same abrupt changes.
Dating is considered secure for some of the Antarctic ice cores.
6) The author suggests that as the world slid in and out of
the last ice age, the general cooling and warming trends were
punctuated by abrupt changes, and climate shifts up to half as
large as the entire difference between ice age and modern
conditions occurred over hemispheric or broader regions in mere
years to decades. Such abrupt changes have been absent during the
few key millennia when agriculture and industry have arisen.
7) In summary, ice-core records indicate that climate
changes in the past have been large, rapid, and synchronous over
broad areas extending into low latitudes, with less variability
over historical times. These ice-core records come from high
mountain glaciers and the polar regions, including small ice caps
and the large ice sheets of Greenland and Antarctica.
-----------
Richard B. Alley: Ice-core evidence of abrupt climate change.
(Proc. Natl. Acad. Sci. US 15 Feb 00 97:1331)
QY: Richard B. Alley [ralley@essc.psu.edu]
-----------
Text Notes:
... ... *firn: The term "firn" refers to the transitional layer
between snow and glacier ice. The layer consists of snow that has
melted during one summer melt season, the layer in the process of
transforming to glacier ice as the temperature decreases.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 14Apr00
For more information: http://scienceweek.com/swfr.htm
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
4. HISTORY OF BIOLOGY:
ON DROSOPHILA AND GENOME RESEARCH
Although biological systems are extremely complex compared to
ordinary physical and chemical systems, one compensation for the
biologist seeking to understand fundamental biological mechanisms
is that the evolution of life on Earth has provided an enormous
variety of distinct biological systems amenable to observation
and experiment. One of the most effective research strategies in
biology has therefore been to work with that biological system
apparently most suited for the solution of the specific problem
under investigation. In the context of molecular biology and
genetics research, one such biological system is the genus
Drosophila, and in particular the species Drosophila
melanogaster. A major advantage of this experimental system is
the presence of giant chromosomes in the insect's salivary
glands. (In cells with chromosomes, the chromosomes are the
physical structure into which DNA is organized and on which genes
are carried.) Drosophila also has a short reproductive cycle
(approximately 10 days), it produces 100 to 400 progeny per
mating, and the organism is easily maintained in the laboratory.
These advantages have combined to make Drosophila melanogaster
one of the most important biological systems in the history of
biology, the system involved in pioneering studies of genetic
mapping, whole genome mutational screens, and functional
alteration of the genome by gene transfer. The complete
sequencing of the Drosophila melanogaster genome was recently
accomplished.
... ... G.M. Rubin and E.B. Lewis (2 installations, US) present a
review of the history of Drosophila in genome research, the
authors making the following points concerning the ground-
breaking Drosophila research by 4 noted researchers in the early
part of the 20th century:
1) In 1910, Thomas H. Morgan (1866-1945), having chosen
Drosophila for his studies of heredity, obtained the first of
many mutants: a white-eyed fly. Morgan was soon joined by 3
principal students: Alfred H. Sturtevant (1891-1970), Calvin B.
Bridges (1889-1938), and Herman J. Muller (1890-1967). Within 5
years, these researchers formulated a revolutionary chromosome
theory of heredity. Their sole experimental method was to do
controlled crosses with mutant flies and count progeny. Morgan
was awarded the Nobel Prize in Physiology and Medicine in 1933.
2) In 1913, Sturtevant constructed the first genetic map and
demonstrated that genes are arranged in linear order.
3) In 1914 to 1916, Bridges provided an elegant first proof
that chromosomes must contain genes and ruled out the alternative
possibility, assumed by some at the time, that chromosomes and
genes were separate hereditary elements.
4) In 1927, Muller demonstrated that ionizing radiation
causes genetic damage and that mutations, including chromosomal
rearrangements, can be induced with x-rays. Muller received the
Nobel Prize in Physiology and Medicine in 1946.
5) In 1935 to 1938, Bridges published chromosome maps of
such accuracy that they are still used today. Making extensive
use of chromosomal rearrangements, Bridges also constructed
cytogenetic maps that assigned genes to specific sections and
even specific bands of the chromosome.
-----------
G.M. Rubin and E.B. Lewis: A brief history of Drosophila's
contributions to genome research.
(Science 24 Mar 00 287:2216)
QY: Gerald M. Rubin, Univ. of Calif. Berkeley 510-642-6000.
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 16Jun00
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
AGAINST PROGRAMMING FUTURE FUNDAMENTAL RESEARCH
Given that science is an enterprise essential to the well-being
of society, the perennial questions are how to fund it, what to
fund, and with how much money? Often, the attitude is that there
is all this money to be used, and with clever policy decisions we
ought to be able to choose and spur the right horse to get us
where we want to go as fast as possible. The difficulty is that
choosing the "right" horse is never obvious, and there is often a
danger that a management process may retard rather than enhance
scientific progress. ... ... Paul Berg and Maxine Singer, in an
opinion piece, consider the dangers of managed science in the
context of modern biology. The authors make the following points:
1) Considering the past 150 years of biological research
(especially genetics), it is clear that success has frequently
been contingent on the choice of the experimental system, and
that often what turned out to be an important experimental system
was first developed on the fringes of science and not in the
mainstream. 2) Mendel's 19th century breeding experiments with
*pea plants defined the early science of genetics, and his work
was first rediscovered at the turn of the century by plant
breeders who contributed to the extension and generalization of
mendelian ideas and to the development of the American corn
industry. 3) By 1914, the fruit fly *Drosophila melanogaster had
displaced corn as the more advantageous organism for genetic
investigation, resulting in the work of T.H. Morgan, A.H.
Sturtevant, C.B. Bridges, H.J. Muller, and their students. 4) At
about 1935, Drosophila proved inadequate to pursue the extant
questions in genetics, and the new experimental system was the
common bread mold *Neurospora crassa, adopted as an experimental
tool by B.O. Dodge, C. Lindegren, G.W. Beadle, and E. Tatum. From
this work came the idea that each gene is responsible for one
enzyme required for the synthesis of a particular cellular
constituent. 5) By the late 1940s, Tatum had adopted a new
experimental system for examining the relation between genes and
cellular functions, the common intestinal bacterium *Escherichia
coli. 6) In the 1950s, attention shifted to still another
experimental system, the viruses (*bacteriophages) that attack
the E. coli bacterium, these viruses having a simpler structure
than bacteria but containing organized genomes. It was the study
of bacteriophages that stimulated Watson and Crick's efforts to
determine the structure of DNA. 7) In the 1960s and 1970s, *yeast
became an experimental system essential to biological research,
with certain yeast genes virtually identical to certain human
genes. 8) More recently, the *nematode worm *Caenorhabditis
elegans has revealed unexpected attributes of the developmental
process, especially the programmed cell death (*apoptosis) of
certain *differentiated cells. 9) Current genetic analysis takes
advantage of decades of work on mutant mice, and recently
genetically altered mice have provided special tools for the
study of gene replacement, very early development, and disease
pathology. 10) Plant genetics research has become a focus again
with attention on the plant *Arabidopsis thaliana, an easily
maintained laboratory plant with a small genome and a rapid life
cycle. The authors conclude: "Nothing in the human-made world
rivals the complexity and diversity of living things. There are,
in nature, concepts that no one has yet imagined. Looking back
over the past 150 years... it seems that the fringes, not the
mainstream, are the most promising places to discover
revolutionary advances. Attempts to program the direction and
tools of genetic research could not have foreseen the diverse
sources from which progress resulted. The lesson is that those
who attempt to program future fundamental research, however well
motivated by medical, agricultural, or social needs, are likely
to divert researchers from the fringes where the most promising
discoveries are often made."
-----------
P. Berg and M. Singer (2 installations, US):
Inspired choices.
(Science 30 Oct 98 282:873)
QY: Paul Berg, Stanford University 415-723-3058.
-----------
Text Notes:
... ... *pea plants: The advantage of Mendel's pea plants was the
possibility of controlled pollination and development of highly
inbred varieties with clearly defined traits. Although it is
often not mentioned, the monk and priest Gregor Mendel (1822-
1884) had training in mathematics and science at the University
of Vienna, and he was in fact a science teacher before his work
with peas began in 1857. When Mendel sent his unpublished paper
to Nageli, an eminent but classical biologist, Nageli was
apparently repelled by the mathematics. Mendel finally published
in 1865 in an obscure journal, the *Transactions of the Brno
Natural History Society*. The work remained ignored and unnoticed
until 1900, when the botanist Hugo De Vries came across the paper
and brought the Mendelian laws of inheritance to the attention of
the scientific world.
... ... *Drosophila melanogaster: See main report.
... ... *Neurospora crassa: In the wild (i.e., natural) state
this mold will grow on a nutrient medium containing sugar as the
only organic compound except for a small required concentration
of biotin. Induced mutations (e.g., produced by x-rays) can
result in mutants that require other organic substances, and
systematic analysis of the genetics of these mutants and their
new requirements made possible an understanding of the genetics
of a number of biochemical pathways and of the enzymes that
control these pathways.
... ... *Escherichia coli: This is a rather ubiquitous bacterium
present in the intestinal tracts of animals, in soil, and in
water. Its advantage as an experimental system is its simple
genetic machinery and rapid growth characteristics. E. coli was
the first animal organism used for cloning and propagating the
genes of other species.
... ... *bacteriophages: Bacteriophage is a virus that
infects bacteria, the virus consisting essentially of a naked
strand of DNA surrounded by a complex polyhedral shell ("capsid")
composed mainly of glycoproteins.
... ... *yeast: Yeast are unicellular fungi that reproduce by
budding. The most important yeast species in research is the
common bread and beer yeast Saccharomyces cerevisiae.
... ... *nematode: An abundant and ubiquitous phylum of
unsegmented roundworms.
... ... *Caenorhabditis elegans: This is a small (1 mm) nematode
worm. It is transparent, hermaphroditic, free-living, and found
in soil. It has a relatively small genome (approximately 3000
genes), and only a few types of cells in its body. It has a 16-hr
embryogenesis that can be achieved in a petri dish, and is thus
highly suitable for the study of developmental and behavioral
genetics.
... ... *apoptosis: In general, the term "apoptosis" refers to
programmed cell death, whether as a part of normal tissue
differentiation and development, or as a program activated in a
defective cell. In the molecular biology of cancer, apoptosis is
the name given to the programmed cell death provoked by the
proteins expressed by tumor suppressor genes. Thus, malignant
cells are defective cells with a deactivated apoptosis program,
and this allows malignant cells to survive and replicate.
... ... *differentiated cells: Refers to developmental cell
specialization (morphology and biochemistry) resulting from
activation (and/or deactivation) of specific parts of the cell
genome.
... ... *Arabidopsis thaliana: (thale cress) A weed of the
mustard family with a small genome of 120 million base pairs.
Arabidopsis is now an important laboratory species, and it is
presently the model for physiological, biochemical, cell
biological, and developmental studies of over 250,000 plant
species.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 20Nov98
For more information: http://scienceweek.com/swfr.htm
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5. MOLECULAR BIOLOGY:
ON BIOMOLECULES AND NANOTECHNOLOGY
Nanotechnology is a branch of applied physical science devoted to
the development of molecular-scale machinery: nanoscale
manipulators, bearings, pumps, computational devices, etc. It is
intriguing that many of the engineering problems in
nanotechnology have already been solved by biological systems as
a consequence of 3 billion years of evolution.
... ... David s. Goodsell (Scripps Research Institute, US)
presents a review of biomolecular machinery of possible interest
in nanotechnology, the author making the following points:
1) Nanoscale manipulators for building molecular-sized
objects were utilized by the earliest biological cells and are
now used by evolved biological cells to build proteins and other
molecules atom by atom according to defined instructions.
Rotating bearing are found in many biological forms. Clamps that
encircle DNA and slide along its length are found in the simplest
bacteria. Many biological cell types contain a rotary motor used
not to power motion but instead to generate energy. Biological
cells use a large collection of molecule-selective pumps to
import ions, amino acids, sugars, vitamins, and all the other
nutrients needed to maintain the cell as a living system.
Biological cells also contain molecular computers that use steric
changes to "read" the concentration of surrounding molecules and
"compute" the proper functional result. By evolutionary search
and modification over trillions of generations, living organisms
have perfected a variety of molecular machines, molecular
structures, and molecular processes.
2) Modular synthesis in biological cells allows proteins to
be built in many shapes and sizes, and most of the processes of
modern biological cells are performed by proteins. But
evolutionary legacy places several limits on the design of
proteins: Proteins are limited to the 20 components encoded in
the DNA genome. Evolution has also limited the size of proteins,
limited proteins to aqueous environments, and has required that
proteins automatically assemble themselves within the crowded
cell interior. But in spite of these limitations, the variety of
protein form and function in modern biological cells is enormous.
3) The size of a protein is essentially limited by the error
rate of the protein-synthesis machinery, which in theory could
produce a protein polymer of any length. "Missense errors", which
involve misreading of the genetic information and substitution of
an incorrect amino acid at one position, occur at an average
frequency of approximately 1 in 2000. For a protein polymer
composed of 500 amino acids, 1 out of 4 proteins will typically
have an error, but nearly every protein of 2000 amino acids will
have an error. More important are "processivity errors", which
cause protein synthesis to abort prematurely. Such errors have
been estimated to occur at a rate of approximately 1 in 3000, so
long proteins of several thousand amino acids are only rarely
constructed in full. The average size of a typical protein chain,
300 to 500 amino acids, is the effective compromise adopted by
most cells. Error rates keep the chain length low, so larger
proteins must be built as complexes of multiple protein chains.
4) The author concludes: "Principles of protein structure
and function... yield insights for nanotechnological design and
fabrication. The diversity of protein structure and function
shows the power of modular, information-driven synthesis, as well
as the limitations imposed by modular design once a dedicated
modular plan is chosen. Proteins demonstrate that extended,
complementary interfaces are essential prerequisites for
molecular self-assembly. The prevalence of protein complexes
proves that error-prone synthesis may be accommodated through the
use of subunits and symmetry to build large objects accurately
and economically. And contrary to our macroscopic experience,
motion and flexibility may be assets, not liabilities."
-----------
David S. Goodsell: Biomolecules and nanotechnology.
(American Scientist May-Jun 2000 88:230
QY: David S. Goodsell, Scripps Research Institute 619-784-1000.
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 16Jun00
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
STRUCTURAL ANALYSIS OF KINESIN MOTOR PROTEIN MOVEMENTS
Fifty years ago, a biologist looking at a large living
biological cell through a light microscope could see motions on
the surface and in the interior of the cell, motions aplenty and
all of it mysterious. It was not until the 1960s that the
microscale structures involved in cell movements were roughly
identified, not until the 1970s that the biochemistry of these
structures was characterized, and not until the 1990s that a
clearer picture of the possible intricate movements of the
"molecular motors" (motor proteins) of living cells became
apparent. An engineer viewing some of the current models of
biological molecular motors will find nanoscale devices involving
only a handful of macromolecules, with each device engaged in a
precise sequence of repetitive movements -- rotations,
vibrations, translocations along tracks, linear contractions,
etc. -- the energy for these motions derived from enzyme-
catalyzed reactions, and all of these devices assembled with
apparent great precision by synthetic processes controlled by
information stored in the genome of the cell. It is quite
understandable if the engineer, for example, while looking at a
model of the macromolecular assembly evidently responsible for
the rotation of a *flagellum, is flabbergasted. We have
apparently crossed a threshold into a world of nanoscale
"machinery" in biological cells, and cell biology in the 21st
century promises to be a source of extraordinary revelations.
The term "microtubules" refers to one of the classes of
filamentous structures that make up the *cytoskeleton found
within the cytoplasm of cells with internal membrane-bound
structures such as a nucleus (eukaryotic cells). Microtubules are
cylinders with a diameter of 25 nanometers, and composed of
repeating subunits of the protein tubulin. Microtubules have many
apparent functions in cells, including directed transport of
small cytoplasmic vesicles, chromosome movements during cell
division, maintenance of cell shape, and movement of flagella and
*cilia. The term "microtubule-based motions" refers to motility
involving microtubules, including motility involving mechanisms
in which microtubules slide relative to one another (as in cilia
and flagella), and the movement of objects along microtubule
tracks (as in transport of vesicles along nerve fibers). Proteins
that interact directly with microtubules apparently serve as
molecular motors in all microtubule-based motions.
"Kinesin" is a motor protein associated with microtubules
and apparently present in all eukaryotic cells. The form of
kinesin originally discovered is a soluble rod-shaped molecule
composed of two polypeptide chains, the molecule travelling
toward one specific end of microtubules (depending on the type of
kinesin, either the so-called "plus" end or "minus" end [*Note
#1]). Kinesin has *adenosine triphosphatase/guanosine
triphosphatase (ATPase/GTPase) activity residing in segments
forming a pair of globular "heads" at one end of the rod, with
various kinesin-type molecules possessing homologous motor
domains attached to different "tails". Kinesin motors apparently
power many cellular motile processes by converting ATP energy
into unidirectional motion along microtubules. Although the
force-generating and enzymatic properties of kinesin have been
extensively studied, the structural basis of movement is unknown.
... ... S. Rice et al (15 authors at 6 installations, US) present
an experimental analysis of the structural change of the kinesin
motor protein, the authors making the following points:
1) Conventional kinesin (the original kinesin isolate) is a
dimer of identical protein chains, each of approximately 120
kilodaltons molecular weight. The dimer is a highly processive
motor that can take more than 100 consecutive 8 nanometer steps
(the distance between 2 specific subunits (alpha/beta) of the
microtubule protein tubulin) before dissociating. Such processive
motion requires coordination between the two motor domains in the
kinesin dimer.
2) The authors report they have detected and visualized a
large conformational change of a region of approximately 15 amino
acids (the so-called "neck-linker region") in kinesin, using a
variety of techniques, including *electron paramagnetic resonance
and *fluorescence resonance energy transfer. The authors report
this region becomes immobilized and extended toward the
microtubule "plus" end when kinesin binds microtubules and ATP,
with the region reverting to a more mobile conformation after
nucleotide hydrolysis. The authors suggest this conformational
change explains both the direction of kinesin motion and
processive movement by the kinesin dimer.
3) The authors conclude: "Our proposed kinesin mechanism
also reveals similarities to other mechanically active enzymes...
A simultaneous requirement of ATP and the partner protein for
triggering a conformational change ensures tight coupling between
ATP-binding energy and mechanical work in all of these enzymes."
-----------
S. Rice et al: A structural change in the kinesin motor protein
that drives motility.
(Nature 16 Dec 99 402:778)
QY: Ronald D. Vale [vale@phys.ucsf.edu]
-----------
Text Notes:
... ... *flagellum: ... A flagellum is a long threadlike
extension providing locomotion for a free-living cell.
... ... *cytoskeleton: The quasi-rigid matrix that among other
things determines cell shape and acts as a scaffold for various
intracellular translocations.
... ... *cilia: The term "cilia" refers to short threadlike
extensions, hundreds usually present on an individual ciliated
cell, the cilia undergoing synchronized movements to produce
locomotion of the cell, or to move extracellular fluid if the
cell is fixed in place.
... ... *Note #1: Microtubules have directionality, in the sense
that the two ends apparently differ chemically, and the
difference can be recognized by certain cell constituents.
According to their organization in the cell, the ends of the
microtubules are labelled as plus or minus.
... ... *adenosine triphosphatase/guanosine triphosphatase
(ATPase/GTPase): Enzymes that hydrolyze ATP and GTP,
respectively. 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 components. GTP is an
important non-protein organic cofactor (a "coenzyme") and enzyme
regulator present in all cells.
... ... *electron paramagnetic resonance: (electron spin
resonance; ESR) This technique is used to investigate
*paramagnetic centers in a molecular system. Only electrons whose
spin is not paired with the oppositely directed spin of another
electron give an ESR signal. With this technique, information can
be obtained about certain transitional ions, free radicals, and
free electron centers. A probe giving an ESR signal can be
attached to proteins to enable otherwise inaccessible systems to
be studied. Through analysis of ESR spectra, rates of molecular
motion and relative orientation of *spin-labeled molecules whose
motion is restrained by surrounding molecules can be determined.
Measurements of rates of molecular motion and molecular
orientation have proved to be important in the study of a variety
of biological problems.
... ... *paramagnetic centers: In general, paramagnetic
substances and groups have a capability to be magnetized which is
slightly greater than that of a vacuum and much less than that of
iron. The paramagnetism is due to the presence of permanent
magnetic dipoles caused by unpaired electron spins.
... ... *spin-labeled molecules: A "spin-label" is a synthetic
paramagnetic organic free radical incorporated in a macromolecule
or assemblage of macromolecules and used, in particular, in
electron paramagnetic resonance spectroscopy.
... ... *fluorescence resonance energy transfer: (fluorescence
energy transfer) Refers to energy transfer between two
fluorophores (chemical groups or molecules capable of
fluorescence). If the two fluorophores are attached to a molecule
at different positions, observations of fluorescence energy
transfer between them can be used to determine the distance
between the two attachment positions.
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 18Feb00
For more information: http://scienceweek.com/swfr.htm
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6. MEDICAL BIOLOGY:
MITOCHONDRIA IN HUMAN DISEASE
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.
In general, the term "apoptosis" refers to programmed cell
death, whether as a part of normal tissue differentiation and
development, or as a program activated in a defective cell. In
the molecular biology of cancer, apoptosis is the name given to
the programmed cell death provoked by certain proteins expressed
by *tumor suppressor genes. Thus, malignant cells are defective
cells with a deactivated apoptosis program, and this allows
malignant cells to survive and replicate. In most tissues within
the body, a delicate balance is maintained between cell
proliferation and cell death. Aging or damaged cells are replaced
with new cells, ensuring that tissues are maintained in prime
condition. If this balance is disturbed in either direction, the
consequences can be severe. Tissue degeneration will occur if
cell death predominates over cell proliferation, and when cell
proliferation outstrips cell death, the result is the development
of tumors.
In recent years, it has been discovered that mitochondria
play a central role in the apoptosis process, this in addition to
their well-established role of providing *adenosine triphosphate
(ATP) to drive the energy-requiring processes within the cell.
... ... Anne Murphy (MitoKor, US) reviews recent research on the
role of mitochondria in human disease, the author making the
following points:
1) Mitochondrial dysfunction is an apparent underlying
contributor to many diseases. It has long been known that the
lack of mitochondrial ATP production can lead to necrotic death
in many pathologies, including *ischemia/reperfusion injury and
*toxin exposure. More recently, it has become apparent that
apoptosis can be induced by a wide variety of events, many of
which involve the release of "apoptogens" (e.g., *cytochrome c
and *caspases) from mitochondria. Often these stimuli initiate a
caspase-dependent cascade of *proteolysis from which cells
generally do not recover.
2) Forms of apoptosis exist that may not be dependent on
mitochondrial apoptogen release. These forms of apoptosis appear
to involve responses to certain *inflammatory mediators that bind
specific death receptors. The extent to which mitochondria play a
role in these varieties of cell death may be dependent upon cell
type and the level of expression of specific caspases.
3) There are numerous diseases with components of apoptosis,
but notable among these are certain neurodegenerative diseases,
ischemic/reperfusion injury, autoimmune disorders and
inflammatory diseases (including arthritis), and viral infection
(including human immunodeficiency virus [HIV])). Also, the
development of certain cancers is apparently associated with the
loss of appropriate levels of apoptosis. Furthermore, in cancer,
resistance of malignant cells to chemotherapeutic agents is
associated with the expression of proteins, localized to
mitochondria, that inhibit apoptosis.
4) Clinical studies have implicated mitochondrial
dysfunction in certain chronic diseases, including *Alzheimer's,
*Huntington's, and *Parkinson's diseases. There is evidence of
metabolic abnormalities in the rates of *glucose utilization and
*lactate production in the affected brain regions of patients
with these diseases. There is also evidence of a decrease in the
maximal activity of *electron-transport-chain complexes in the
brains or peripheral tissues of patients with these diseases. The
question is whether these defects are sufficient to compromise
normal neuronal function, and whether they are the cause or the
result of the respective disease.
-----------
Anne Murphy: Mitochondria in human disease.
(The Biochemist April 2000)
QY: Anne Murphy [murphya@mitokor.com]
-----------
Text Notes:
... ... *electron transport: This refers to a sequence of steps
in the final stage of the aerobic respiration biochemical pathway
in which high energy electrons are effectively passed through a
series of membrane-bound carrier molecules to support a proton
gradient involved in energy storage. The term "transport" here
refers essentially to a chemical flow diagram and not necessarily
to an actual spatial translocation of electrons.
... ... *oxidative metabolism: In general, a set of biochemical
pathways dependent on the utilization of supplied oxygen.
... ... *symbiotic: In biology, "symbiosis" is an intimate and
protracted association of individuals of different species.
... ... *tumor suppressor genes: In general, cancer genes have
been divided into 2 classes, proto-oncogenes and tumor suppressor
genes. Proto-oncogenes are genes that sustain activating changes
in human cancer. These changes may take the form of point
mutations or gene rearrangements that lead to increased or
uncontrolled activity of the encoded protein, or they make take
the form of gene amplification, which results in increased levels
of protein expression. In contrast, tumor suppressor genes are
characterized by inactivating changes in human cancer, typically
point mutations that result in truncation or functional
inactivation of the encoded protein, or gross deletions of
chromosomal fragments carrying these genes.
... ... *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.
... ... *ischemia/reperfusion injury: In general, "ischemia" is a
sudden loss of blood supply to a tissue caused by blockage of a
blood vessel. The term "ischemia/reperfusion injury" refers to
the damage that can occur to a tissue when it is reperfused after
a prolonged period of ischemia. The phenomenon is of considerable
clinical importance, especially in connection with heart attacks
and strokes.
... ... *toxin: In general, any noxious or poisonous substance,
especially substances produced by living systems.
... ... *cytochrome c: The cytochromes, categorized as
hemoproteins with differing porphyrin groups, are widely
distributed respiratory (oxygen-utilizing) catalysts involved in
the electron transport chain of living cells. They do not combine
with substrates, but alternate between Fe(2+) and Fe(3+) states.
There are various cytochromes, with cytochrome c present in the
greatest amounts, and most importantly in the mitochondria of
eukaryotic cells.
... ... *caspases: Proteases are a class of enzymes that
hydrolyze proteins, splitting them into various groups of
subunits, with the sites of hydrolysis dependent on the
particular enzyme and the protein substrate, and a caspase is a
type of protease implicated in apoptosis.
... ... *proteolysis: In general, hydrolysis (breakdown) of
proteins.
... ... *inflammatory mediators: In general, an "inflammatory
change" is a response of tissues to irritation or injury. The
response involves a dynamic complex of cellular and chemical
reactions that occur in the affected blood vessels and adjacent
tissues.
... ... *Alzheimer's, *Huntington's, and *Parkinson's diseases:
All three of these neurodegenerative diseases involve
considerable loss of nerve cells in certain areas of the brain.
... ... *glucose utilization: In biological systems, glycolysis
(also known as Embden-Meyerhof pathway), involving the breakdown
of glucose, is one of the main energy producing pathways in the
cell.
... ... *lactate production: Lactate is a salt or ester of lactic
acid, and lactic acid is a common end product of glycolysis in
biological systems.
... ... *electron-transport-chain complexes: The term "electron-
transport chain" (respiratory chain) refers to the sequence of
reactions involving enzymes and other proteins within the
mitochondrion by which substrates are oxidized.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 16Jun00
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
MOLECULAR BIOLOGY: APOPTOSIS, MITOCHONDRIA, AND CASPASES
Apoptosis (programmed cell death) is a rapid and specific process
involving the production of a number of enzymes in the cell
programmed to be destroyed. This programmed destruction is not
always harmful, or always the result of cellular damage of one
sort or another. In humans, for example, the lack of webbing
between fingers and toes is a result of apoptosis of cells of
webbing tissue occurring during embryological development, the
apoptosis in this case being a normal part of the larger
embryological program. In the mature organism, apoptosis is the
usual method of removing damaged cells after these cells are
recognized to be damaged by one mechanism or another. It is known
that normal cells carry an apoptosis receptor on their surfaces,
called CD95, and that when this surface receptor is cross-linked
by its specific ligand, this triggers the sequence of events
known as apoptosis. In the apoptosis sequence, certain
*proteolytic enzymes inside the cell are activated, and in
addition a variety of lipids that cause cell dysfunction are
synthesized.
... ... D.R. Green and J.C. Reed review the involvement of
*mitochondria with apoptosis in *metazoan cells, and the authors
make the following points: 1) The current consensus among
biologists is that approximately 2 billion years ago the cells
destined to become the ancestors of all *eukaryotes entered into
a partnership with an ancestor of today's *purple bacteria, an
ancestor that subsequently became the mitochondria of today. 2)
It has been hypothesized by several investigators that the
*endosymbiotic origins of mitochondria and the evolution of
aerobic metabolism in eukaryotes formed the basis for the
evolution of active cell death, which in metazoans is manifested
predominantly as apoptosis. Central roles for mitochondria as the
orchestrators of apoptosis have been firmly established in many
systems. 3) In recent years it has become apparent that the
effectors of apoptosis are a family of intracellular proteases
known as caspases, although inhibiting these enzymes does not
always prevent apoptosis. 4) At least 3 general mechanisms have
been proposed for the involvement of mitochondria in the control
of cell life and death: a) disruption of *electron transport,
*oxidative phosphorylation, and adenosine triphosphate (ATP)
production; b) release of proteins that trigger activation of the
caspases family of proteases; c) alteration of cellular *redox
potentials. 5) In many apoptosis scenarios, the mitochondrial
inner electrical transmembrane potential collapses, indicating
the opening of large conductance channels through the inner
membrane. In contrast, certain stimuli can induce rupture of the
outer membrane of mitochondria and release of caspase-activation
proteins. The authors conclude: "Perhaps a few hundred million
years ago, either convergent or divergent evolutionary processes
allowed the ... fundamental framework for bacterial warfare to be
incorporated into the cell death mechanisms used by animal cells,
thereby establishing mitochondria as important participants not
only in animal cell life but also in active cell death."
... ... In a companion and contiguous review of caspases and
apoptosis, N.A. Thornberry and Y. Lazebnik point out the
following: 1) Proteolysis is irreversible, which implies that
regulation of proteases is limited to control of their activity
and availability of substrate -- the only known way of
"correcting" a cleaved protein is to make it afresh. 2) Most
proteases are synthesized as precursors that have little if any
catalytic activity. The precursor is usually converted to the
active enzyme by proteolytic processing mediated either by
another protease or by autocatalysis. Thus large amounts of
precursor can be accumulated in advance and activated on demand.
3) Proteases can regulate their own activation, resulting in an
exponential rate of activation. 4) Where there are proteases
there are inhibitors, and these inhibitors regulate the
concentration of active protease in the cell. 5) Proteolytic
reactions can be specific, determined by a combination of
primary, secondary, or tertiary structures of protein substrates.
Proteolysis that governs critical biological processes such as
the cell cycle or cell death is highly specific and involves a
restricted set of substrates. 6) The various caspases share
similarities in amino acid sequence, structure, and substrate
specificity. 7) Caspases are among the most specific of proteases
with an unusual and absolute requirement for cleavage after
aspartic acid and recognition of at least 4 amino acids terminal
to the cleavage site. 8) The strict specificity of caspases is
consistent with the observation that apoptosis is not accompanied
by indiscriminate protein digestion, but rather a select set of
proteins is cleaved in a coordinated manner, usually at a single
site, resulting in a loss or change in function. 9) Apoptotic
events include DNA fragmentation, *chromatin condensation,
*membrane blebbing, cell shrinkage, and disassembly into
membrane-enclosed vesicles (apoptotic bodies). In vivo, this
process culminates with the engulfment of apoptotic bodies by
other cells, preventing complications that would result from a
release of intracellular contents. In apoptosis, these changes
occur in a predictable reproducible sequence and can be completed
with 30 to 60 minutes. The authors conclude: "Substantial
progress has been made in understanding the structural and
catalytic properties of active caspases and their contribution to
apoptosis. The goal for future research is to understand the
regulation of these enzymes. This should facilitate efforts to
rationally manipulate the apoptotic machinery for therapeutic
gain."
-----------
D.R. Green and J.C. Reed (2 installations, US): Mitochondria and
apoptosis.
(Science 28 Aug 98 281:1309)
QY: Douglas R. Green, La Jolla Institute for Allergy and
Immunology, 10355 Science Center Drive, San Diego, CA 92121 US.
-----------
N.A. Thornberry and Y. Lazebnik (2 installations, US): Caspases:
enemies within.
(Science 28 Aug 98 281:1312)
QY: Nancy A. Thornberry, Merck Research Laboratories, Rahway, NJ
07065 US.
-----------
Text Notes:
... ... *proteolytic enzymes: These enzymes, also called
"proteases", split proteins and thereby degrade them. The enzymes
catalyze the hydrolysis of peptide bonds, fragmenting proteins
into polypeptide chains, and fragmenting polypeptide chains into
constituent amino acids. Sometimes proteolytic enzymes and
proteases are distinguished, with the term "proteases" reserved
for proteolytic enzymes with high specificity for peptide bonds
between particular amino acids.
... ... *mitochondria: See main report.
... ... *metazoan cells: Metazoans are multicellular animals.
... ... *eukaryotes: Cells (and organisms consisting of such
cells) that contain intracellular membrane-bound compartments
such as a nucleus (membrane-bound "organelles").
... ... *purple bacteria: Specifically, any of the various
photosynthetic bacteria that contain bacteriochlorophyll, and are
thus distinguished by purplish or reddish-brown pigments. But the
term "purple bacteria" is sometimes used as a synonym for the
phylum Proteobacteria, a general category comprising a large
number of diverse forms.
... ... *endosymbiotic: Endosymbiosis is an arrangement in which
one organism lives inside another organism, but the term is
usually restricted to arrangements of mutual benefit, thus not
including parasite-host relationships. A number of eukaryotic
cell organelles (including mitochondria) are believed to have
originated from endosymbiotic relationships between eukaryotic
cells and simpler cells.
... ... *electron transport: See main report.
... ... *oxidative phosphorylation: Production of ATP during
aerobic respiration. It takes place in the mitochondria of
eukaryotic cells and requires molecular oxygen as a terminal
electron acceptor.
... ... *redox potentials: Chemical potentials in a chemical
reaction involving the simultaneous reduction and oxidation of
two compounds by a transfer of electrons between them.
... ... *chromatin: The entire complex of a eukaryotic
chromosome, including DNA, chromosomal proteins, and chromosomal
RNA.
... ... *membrane blebbing: Refers to the macroscopic blistering
of the surfaces of cells when they die under certain conditions.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 2Oct98
For more information: http://scienceweek.com/swfr.htm
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7. IN BRIEF: OF GENES AND MONEY
These days, many molecular biologists have one eye on a computer
screen showing an analysis of experimental data, and another eye
on a television screen showing a moving stock market ticker tape.
That is the way it is. Possible commercial applications of
research in molecular biology now surround many laboratories like
golden halos. Millions, hundreds of millions, and billions of
dollars in personal riches are at stake, and recent events
surrounding the sequencing of the human genome are a good example
of the approximate circus atmosphere that now pervades this
corner of science. The Editors recommend a long article by
Richard Preston titled "The Genome Warrior" in the New Yorker of
June 12, 2000. Although the article has a few errors of fact
(buffer is not "a type of purified salt water", but any solution
containing substances designed to keep the pH of the solution
constant), it is worth reading. But be warned: The personality
collisions and financial gyrations described in the article may
make you dizzy.
-------------------
SCIENCE-WEEK http://scienceweek.com 16Jun00
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8. IN FOCUS: ENERGY AND THE DEATH OF LIVING SYSTEMS
"It seems obvious that life requires a continuous supply of
energy, and that an interruption of that supply inevitably leads
to death. However, as in a good murder mystery, things are not
always as they seem. The intimate relation between energy and
death is complex. Energy depletion may be one of the most common
causes of cell death, but this death may take many different
forms in different tissues and conditions, and is far from
simple. Some forms of cell death, such as *apoptosis and
*autophagy, require energy, and are blocked in its absence, but
energy depletion may also trigger apoptosis. *Mitochondria, those
cellular bugs that we thought were living in benign *symbiosis
with our cells, have recently been implicated as the chief
suspects in triggering cellular death and dysfunction. A trail of
clues leads back to the mitochondria, implicating them in
apoptosis, *necrosis, *excitotoxicity, degenerative diseases, and
aging itself. This is an impressive list of death and destruction
for a venerable organelle that we thought was benignly producing
most of our cellular energy. It has even been half-seriously
suggested that by some that we rename mitochondria
'necrochondria'."
-----------
[Editor's note: For more on mitochondria, see report #6, this
issue.]
-----------
Guy Brown: "Energy, life and death."
in: _The Biochemist_ April 2000
-----------
Text Notes:
... ... *apoptosis: In general, programmed cell death produced by
control mechanisms designed to destroy defective cells.
... ... *autophagy: Intracellular segregation and disposal of
damaged organelles.
... ... *Mitochondria: 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 cells with internal membrane-bound
organelles (eukaryotic cells) may contain from a few to several
thousand mitochondria in each cell type. The mitochondria are
relatively large cylindrical structures up to 10 microns long and
up to 2 microns in diameter, and they are believed to have
originated as organisms that became symbiotic with eukaryotic
cells. In biology, "symbiosis" is an intimate and protracted
association of individuals of different species.
... ... *symbiosis: See previous note.
... ... *necrosis: In general, pathological death of one or more
cells, or of a portion of a tissue or organ.
... ... *excitotoxicity: In general, excitotoxicity is a toxicity
that involves a primary stage of excitation of cells or tissues
followed by the poisoning of these cells or tissues.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 16Jun00
For more information: http://scienceweek.com/swfr.htm
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