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ScienceWeek
SCIENCE-WEEK
A Weekly Digest of the News of Science
August 28, 1998
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There are living systems, there is no "living matter".
-- Jacques Lucien Monod (1910-1976)
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Contents of This Issue:
1. On the Overproduction of US Biomedical Researchers
2. Stellar Circular Polarization and Biomolecular Homochirality
3. On the Solar System Oort Cloud
4. Biotechnology: Synthetic Secretory Granules
5. Protein Architecture: Hidden Sequence Periodicities
6. Origin of Life: Production of Peptides on Inorganic Surfaces
7. Molecular Biology: An Integrated Transcription Complex Model
8. On the Permian Extinction and the Greenhouse Effect
9. Alzheimer's Disease: Interhemispheric Disconnection Syndrome
10. Kaposi's Sarcoma: Further Evidence for Role of Herpesvirus
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1. ON THE OVERPRODUCTION OF US BIOMEDICAL RESEARCHERS
There are always practical problems concerning the training of
scientists, but two persistent questions are How many? and Where
do they work? Marincola and Solomon (2 installations, US), in a
recent editorial in the journal *Science*, review the current
problems in the training of biomedical research scientists (and
propose a solution), but the ideas are perhaps just as applicable
to physics and chemistry. The authors make the following points:
1) Although the number of biomedical research trainees in the US
has expanded considerably over the past 20 years, the number of
tenured positions is declining. 2) The average time to obtain a
PhD rose from 4.4 years in the 1970s to 5.6 years in the 1990s.
3) Each principal investigator trains many times the single
scientist required to replace himself or herself. This intrinsic
instability could threaten the profession. 4) Many researchers
perceive that science is thriving at increasing and unacceptable
cost to those being trained. In strictly economic terms, it is in
the interest of senior investigators to maintain the number of
trainees, who work long hours in large numbers for little pay
over many years in return for the chance to develop a satisfying
career. 5) A solution may be to uncouple scientific productivity
from an investigator's ability to attract and employ trainees --
the creation of permanent research positions for scientists who
would neither compete for grants nor train others. They would be
supported through investigators who hold traditional academic
appointments. The authors give as an example the institution of
3-year positions for researchers at the Scripps Institute (US).
The essential idea, then, is the amplification of the number of
already existing non-tenure "research associate" positions, these
positions to be filled by PhDs on a continuing short-term
contract basis. The authors state: "This career track could be
recognized explicitly, legitimized, and nourished to become an
element of the research enterprise." The editorial does not
address the question of how this two-tier structure will satisfy
the career objectives of young scientists who are first-rate, but
because of lack of employment opportunities, are forced into the
second tier.
QY: Elizabeth Marincola
(Science 31 Jul 98 281:64) (Science-Week 28 Aug 98)
2. STELLAR CIRCULAR POLARIZATION AND BIOMOLECULAR HOMOCHIRALITY
Electromagnetic radiation involves the propagation of both
electric and magnetic forces, and at each point in a light beam,
there is a component electric field and a component magnetic
field, both of which oscillate in all directions perpendicular to
each other and to the direction in which the beam is propagated.
In plane-polarized light, the component electric field oscillates
as in ordinary light except that the direction of oscillation is
contained within a plane. Likewise, in plane-polarized light, the
component magnetic field oscillates within a plane, the planes in
question being perpendicular. Circularly polarized light has a
component electric field that varies in direction but not in
magnitude, so that the field traverses a spiral path in either a
clockwise or counterclockwise direction. In the laboratory, high
levels of *enantiomeric excess in *racemic substances can be
produced by asymmetric photolysis by circularly polarized light.
Biological molecules exhibit extensive *homochirality (e.g.,
living systems use almost exclusively L-amino acids and D-
sugars), and this has been a puzzle since its discovery in the
19th century. It has been suggested that homochirality may be a
prerequisite for the origin of life, and a number of processes
have been proposed that may have produced enantiomeric excess in
prebiotic organic molecules, including the action of circular
polarization from the daylight sky, but these effects are
considered too small to account for homochirality. Another view
is that the origin of homochirality is extraterrestrial, and
apparent support for this view has been provided by the recent
discovery of an excess of L-amino acids in the *Murchison
meteorite. ... ... Bailey et al (8 authors at 4 installations, AU
UK FR JP) now report strong infrared circular polarization
resulting from dust scattering in *reflection nebula in an Orion
star formation region (OMC-1), and the authors suggest that
circular polarization at shorter wavelengths might have been
important in inducing chiral asymmetry in interstellar organic
molecules that could be subsequently delivered to the early Earth
by comets, interplanetary dust particles, or meteors. The authors
suggest this could account for the excess of L-amino acids found
in the Murchison meteorite, and could explain the origin of the
homochirality of biological molecules. The authors conclude:
"Whether a very high enantiomeric excess is a prerequisite for
the origin of life, or a very small effect is amplified in the
process, the ultimate source [of the excess] is likely to be of
extraterrestrial origin."
QY: Jeremy Bailey, Anglo-Australian Observatory, PO Box 296,
Epping, New South Wales 2121, AU.
(Science 31 Jul 98 281:672) (Science-Week 21 Aug 98)
-------------------
Related Background:
... ... *enantiomeric: In chemistry, an enantiomer is a compound
whose structure is not superimposable on its mirror image, the
compound being one of a pair of optical isomers, each of which
interacts differently with polarized light (i.e., shows optical
activity). A mixture of two optical isomers in equal amounts is
called a *racemic mixture, and racemic mixtures do not show
optical activity. A reactant or process that produces an
enantiomeric excess is simply a reactant or process that produces
or selects one enantiomer in excess over the other enantiomer.
... ... *racemic: (see *enantiomeric)
... ... *homochirality: Chirality is a property of certain
asymmetric molecules (or of any object), the property being that
the mirror images of the molecules cannot be superimposed one on
the other while facing in the same direction. Homochirality is
the preference of a process or system for a single optical isomer
in a pair of isomers.
... ... *Murchison meteorite: This meteorite, which fell near
Murchison AU in 1969, contains 8 amino acids and the nucleotide
bases adenine, guanine, and uracil.
... ... *reflection nebula: A bright cloud of interstellar gas
and dust that lies in the vicinity of a star or stellar group,
with the starlight scattered in all directions by the dust
grains, and the scattered light visible because of the high
density of the dust.
-------------------
Related Background:
POSSIBLE EXPLANATION FOR LEVOROTATORY AMINO ACIDS IN BIOlOGY
A chiral molecule is an asymmetric molecule that cannot be super-
imposed on its mirror image. The molecule has two forms, called
enantiomorphs, that are mirror images of each other, the solut-
ions of which rotate the plane of polarized light in different
directions, left or right, making the enantiomers levorotatory or
dextrorotatory. Only levorotatory amino acids are present in
biological systems, and the reason for this is unknown. M. H.
Engel and S. A. Macko (University of Oklahoma, US; University of
Virginia, US) now report that individual amino-acid enantiomers
from the Murchison meteorite contain higher concentrations of the
nitrogen isotope N(15) compared to similar materials on Earth.
The authors suggest this confirms an extraterrestrial source for
an L-enantiomeric excess in our solar system that may predate the
origin of life on Earth.
QY: M. H. Engel
(Nature 18 Sep 97) (Science-Week 3 Oct 97)
3. ON THE SOLAR SYSTEM OORT CLOUD
In general, a comet is a kilometer-size chunk of ice and
associated dust and debris. The *Oort cloud is an apparent
spherical shell of comets 10,000 to 100,000 *AU from the Sun and
the proposed source of comets that orbit the Sun. The cloud is at
the extreme edge of the Sun's influence, halfway to the nearest
star, and it is believed that when the cloud is perturbed by
passing stars, comets may be sent into a solar orbit. The size
and structure of the Oort cloud have been deduced from
statistical studies of the orbits of comets; there is no direct
evidence for the cloud's existence. ... ... Paul R. Weissman (Jet
Propulsion Laboratory, US) reviews the history and dynamics of
the Oort cloud, and makes the following points: 1) Three main
questions are of concern in current Oort-cloud research. First,
What is the cloud's structure? The present idea is that comets at
the outer edge of the cloud are rapidly lost, either to
interstellar space or to the inner solar system, because of
stellar and molecular-cloud perturbations. But deeper inside the
cloud there is probably a relatively dense core that slowly
replenishes the outer regions. 2) The second main question is,
How many comets inhabit the cloud? To account for the observed
number of long-period comets (which are believed to have origin
in the Oort cloud), astronomers now estimate the cloud contains 6
x 10^(12) comets, making Oort-cloud comets the most abundant
substantial bodies in the solar system. If the best estimate for
the average mass of a comet -- approximately 4 x 10^(10) metric
tons -- is applied, the total mass of comets in the Oort cloud is
approximately 40 times that of Earth. 3) The third main question
is, From where did the Oort cloud comets originally come? The
present consensus is that the only possible origin is the
planetary system. 4) Space missions scheduled for launch within
the next few years are expected to provide important information
concerning specific comets and their origins. The author
concludes: "The new millennium is going to be a wonderful time
for studying comets."
QY: Paul R. Weissman, Jet Propulsion Laboratory 818-395-6811.
(Scientific American August 1998) (Science-Week 28 Aug 98)
-------------------
Related Background:
... ... *Oort cloud: The cloud is named after Jan Hendrik Oort
(1900-1992). Oort first proposed the existence of the cloud in
1950. In 1927, Oort calculated the mass and size of the Galaxy,
and the distance of the Sun from its center, from the observed
movements of the stars around the center.
... ... *AU: Astronomical Unit. 1 AU = the mean distance from the
Sun to the Earth = approximately 93 million miles, and exactly
149,597,870 kilometers.
-------------------
Related Background:
AN ASTEROID-LIKE OBJECT EVIDENTLY FROM THE OORT CLOUD
... Object 1996PW is a 10-kilometer entity that appears to be an
asteroid, lacking the gaseous emissions and dusty coma of a
comet. Now Paul Weissman (discover of 1996PW) and Harold Levison
(Jet Propulsion Laboratory, Pasadena CA US; Southwest Research
Institute, Boulder CO US) have run computer simulations of the
history of the orbit of 1996PW, and they conclude the orbit was
at one time much larger and extended to the Oort cloud. They also
conclude the object has orbited the sun only 27 times. If 1996PW
is indeed an asteroid and not a comet, its presence in the Oort
Cloud is puzzling.
QY: Paul Weissman, Jet Prop. Lab., Pasadena CA 818-395-6811.
(Astrophys. J. 20 Oct 97) (Science-Week 31 Oct 97)
4. BIOTECHNOLOGY: SYNTHETIC SECRETORY GRANULES
Biological cells that secrete various substances (secretory
cells) contain submicroscopic granules composed of a polyanionic
polymer network that is collapsed owing to the presence of
hydronium ions and weak base cations. The network is encapsulated
within a lipid membrane, and functions as a vehicle for the
osmotically inert storage of a variety of granule-bound
endogenous mediator species, such as histamine, serotonin, and
proteases. These species are excreted from the granule and thence
from the cell in response to external biochemical signals.
... ... Kiser et al (3 authors at 3 installations, US) report the
systematic engineering of multi-component, environmentally
responsive *hydrogel microspheres coated with a lipid bilayer to
mimic more closely the natural secretory granule. These
microspheres exhibit pH- and ion-dependent volume phase
transitions and ion-sensitive exchange of bound cations when the
encapsulating lipid membrane is perforated (porated). The authors
stimulated perforation electrically in individual microgel
particles immobilized and manipulated with a micropipette. They
suggest this system could find use for the triggered release of
encapsulated drugs in the body, including the use of nanometer-
size gel particles small enough to pass through permeable tumor
vasculature into tumor tissue for uptake by tumor cells.
QY: David Needham
(Nature 30 Jul 98 394:459) (Science-Week 28 Aug 98)
-------------------
Related Background:
... ... *hydrogel: In this report, the anionic hydrogel is
composed of a 1:4 mole ratio of methylene-bis-acrylamide and
methacrylic acid, prepared by a precipitation polymerization
method. The hydrogel microspheres had a diameter of 6.5 microns
at pH 7.
-------------------
Related Background:
ON DRUG DELIVERY AND TARGETING
R. Langer (Massachusetts Institute of Technology, US) reviews the
current status of drug delivery and target systems. When a
pharmaceutical agent is encapsulated within, or attached to, a
polymer or lipid, drug safety and efficacy can be greatly
improved and new therapies are possible. This has provided the
impetus for active study of the design of degradable materials,
intelligent delivery systems, and approaches for delivery through
different portals of the body. Delivery systems that could target
drugs to specific body sites or precisely control drug release
rates for prolonged times have long been dreamed of, but only in
recent years has the development of such systems become
practical. In a short time, new drug delivery systems have had an
impact on nearly every branch of medicine. There are 3 general
mechanisms by which drugs are delivered from polymer or lipid
systems: 1) diffusion of the drug species from or through the
system; 2) a chemical or enzymatic reaction leading to
degradation of the system, or cleavage of the drug from the
system; 3) solvent activation, either through osmosis or swelling
of the system. The author suggests that with the progress being
made in biology, chemistry, biomaterials science, and engineering
and pharmaceutical sciences, this field should have a bright and
rapidly evolving future.
QY: Robert Langer, Mass. Inst. of Technology 617-253-1000.
(Nature 30 Apr 98 392/supp:5) (Science-Week 29 May 98)
5. PROTEIN ARCHITECTURE: HIDDEN SEQUENCE PERIODICITIES
The rapidly growing database of experimentally determined protein
structures has provided new insights into the characteristics of
the architectures into which protein domains can fold. It has
become clear that there exists a broad range of folds available
to proteins, and it is accepted dogma that the choice of fold is
dictated by amino acid sequence. In parallel with these
developments, there has been intensive study of protein
sequences, and one aspect of this work has been a series of
papers by various authors on the longitudinal correlation
properties of sequences. These studies are interpreted to
indicate that by various criteria protein sequences exist in a
manner indistinguishable from random. Taken together, these
results pose a riddle. Consider, for example, the fact that a
significant number of protein architectures exhibit structural
symmetry. If structure is determined by sequence, there must be
signals in the sequences of these molecules that dictate their
structural symmetry. Furthermore, because it is unreasonable to
suppose that symmetrical proteins fold differently from less
ordered proteins, one may justifiably presume that such
architecture signals are a general feature of protein sequences.
If, however, the sequences of proteins are truly longitudinally
random, no such signal can exist. ... ... S. Rackovsky (Mount
Sinai School of Medicine New York, US) reports a mathematical
analysis of the problem, the method involving the assemblage of
groups of sequences associated with well-defined architectures,
the groups chosen so that they were not closely homologous, and
the isolation of sequence signals by means of Fourier analysis of
the physical properties of the amino acids in these sequences.
The author reports the following results: 1) Protein sequences
are not random. They exhibit periodic signals in various physical
properties that are statistically significantly different from
what one would expect from random sequences. 2) Distinct sets of
sequence signals characterize individual protein architectures.
3) These sequence signals can occur in any amino acid property.
It is the frequency of the signals, rather than the physical
property in which they occur, that determines the architecture.
QY: S. Rackovsky
(Proc. Natl. Acad. Sci. US 21 Jul 98 95:8580)
(Science-Week 28 Aug 98)
-------------------
Related Background:
ON THE THERMODYNAMIC HYPOTHESIS OF PROTEIN FOLDING
Proteins are macromolecules that assume specific high-order
configurations, with each type of protein molecule folding into
the specific configuration necessary for its function. There are
two central aspects of this folding: it occurs extremely rapidly,
on the order of milliseconds to minutes after first synthesis of
the polymer, and the final configuration achieved is always
identical for each type of protein. Thus, protein A rapidly folds
into the protein A-conformation, and protein B rapidly folds into
the protein B-conformation. The question is how does this happen?
What are the variables that control these events? Experimental
techniques in the study of protein folding often involve
"denaturation" and "renaturation" of proteins in vitro.
Denaturation is the elimination of the folding of a protein by
changing ambient conditions such as temperature and pH, and
renaturation is the refolding of the protein molecule into the
native state following restoration of the original ambient
conditions. ... ... Govindarajan and Goldstein (University of
Michigan, US) present a theoretical analysis of current ideas
concerning protein folding. In 1969, C. Levinthal pointed out
that it is impossible for an unfolded protein to find the native
state (its final configuration) by randomly searching through the
entire space of possible conformations. This led Levinthal to
postulate that a protein must follow a specific path to the final
configuration, and therefore folding must be under kinetic
control (i.e., under the control of a specific sequence of
reactions). According to Levinthal, if the final folded state
turned out to be one of lowest configurational energy, it would
be a consequence of the biological evolution of specific chemical
reaction sequences ("kinetic control"), and not of physical
chemistry and the laws of thermodynamics ("thermodynamic
control"). In contrast to this idea of Levinthal, C. Anfinsen in
1973 concluded from the results of his numerous denaturation-
renaturation experiments that the native state of the protein is
indeed the global minimum of free energy, a conjecture that he
called the "thermodynamic hypothesis" of protein folding. The
debate between these two viewpoints of kinetic control and
thermodynamic control has continued for more than two decades,
with numerous experimentalists and theoreticians investigating
whether proteins reach their global free energy minimum in a
pathway-independent manner under thermodynamic control, or
whether the protein molecule follows a specific pathway to a
possibly local free energy minimum under kinetic control.
Govindarajan and Goldstein now report an exploration of the
validity of the thermodynamic hypothesis of protein folding by
simulation of the evolution of protein sequences, investigating
whether what is proposed by the thermodynamic hypothesis could
result through the process of protein evolution, the approach
involving certain assumptions concerning the effects of random
mutations on protein evolution. The authors report that their
results suggest that even if protein folding is under kinetic
control, a specific kinetic sequence will evolve so that the
native state of the protein molecule is most often the state of
minimum free energy. They point out that one consequence of this
is that theoretical methods that predict protein structure by
means of algorithms and search strategies not apparently
available to the protein itself may still be relevant as long as
the model produces an eventual state of minimum free energy.
QY: Richard A. Goldstein (richardg@umich.edu)
(Proc. Natl. Acad. Sci. US 12 May 98 95:5545)
(Science-Week 26 Jun 98)
-------------------
Related Background:
BROWNIAN DYNAMICS SIMULATIONS OF PROTEIN FOLDING
Protein folding occurs on a time scale ranging from milliseconds
to minutes for a majority of proteins. Computer simulation of
protein folding, from a random configuration to the native
structure, is nontrivial due to the large disparity between the
simulation and folding time scales. In order to overcome this
limitation, simple models with idealized protein subdomains,
e.g., the diffusion-collision model, have gained some popularity.
The diffusion-collision protein-folding mechanism postulates the
early-stage formation of fluctuating quasiparticles (micro-
domains), which may be incipient secondary structures (alpha-
helices and beta-sheets) or hydrophobic clusters. These micro-
domains move via diffusion, and their coalescence leads to the
formation of folded proteins. Thus, the diffusion-collision model
reduces the complexity of the folding process from a consider-
ation of individual amino acids to that of the properties of a
few microdomains and their interactions. ... ... Rojnuckarin et
al (3 authors at 2 installations, US) present an analysis of the
folding of a 4-helix protein bundle within the framework of a
diffusion-collision model. Even with the simplifying assumptions
of a diffusion-collision model, a direct application of standard
Brownian dynamics methods would consume 10,000 processor-years on
current supercomputers. The authors circumvented this difficulty
by invoking a special Brownian dynamics simulation. They report
that a coarse-grained (i.e., crude) model of the 4-helix bundle
can be simulated in several days on current supercomputers, and
that such simulations yield folding times that are in the range
of time scales observed in experiments.
QY: Sangtae Kim (kim01@aa.WL.com)
(Proc. Natl. Acad. Sci. US 14 Apr 98 95:4288)
(Science-Week 15 May 98)
6. ORIGIN OF LIFE: PRODUCTION OF PEPTIDES ON INORGANIC SURFACES
The primordial process responsible for the activation of amino
acids and the formation of peptides under primordial conditions
is one of the great riddles of the origin of life. ... ... Huber
and Wachterschauser (Technische Universitat Munchen, DE) now
report that in experiments modeling volcanic or hydrothermal
settings, amino acids were converted into their peptides by use
of coprecipitated (Ni,Fe)S and CO in conjunction with H(sub2)S
(or CH(sub3)SH) as a catalyst and condensation agent at 100
degrees centigrade and pH 7 to 10 under anaerobic aqueous
conditions. The amino acids involved in the experiments were
phenylalanine, tyrosine, and glycine. The authors suggest their
results demonstrate that amino acids can be activated under
geochemically relevant conditions, and that the results support a
thermophilic origin of life with a primordial surface metabolism
on transition metal sulfide minerals. They further suggest that a
continuously recycling library of peptides was generated on the
surfaces of a library of (Fe,Ni)S structures, and that the
results raise the possibility that CO and Ni had a much greater
role in the primordial metabolism than in any of the known extant
metabolisms. They point out that all known extant organisms are
found in habitats with low activities of CO and Ni, and they
suggest this could explain why organisms resorted to the
formation of CO from CO(sub2) and to the elimination of nickel
from many enzymes.
QY: Gunter Wachterschauser, Tal 29, D-80331 Munchen, DE.
(Science 31 Jul 98 281:670) (Science-Week 28 Aug 98)
-------------------
Related Background:
PREBIOTIC ORGANIC COMPOUNDS: OCEANIC PROTECTION FROM SOLAR UV
It is generally believed that the Earth's primitive atmosphere
lacked oxygen, and therefore that an ozone layer protective
against ultraviolet radiation did not exist. This is considered
to be a serious problem for the accumulation of prebiotic organic
compounds on Earth and on Mars, and this problem would have been
worsened by the theoretically expected elevated ultraviolet
radiation production of the early Sun. Protection from
ultraviolet radiation is one of the motivations for proposing an
origin of life in submarine vents, benthic regions, and in deep
subsurface environments. Most attempts to deal with this problem
have involved atmospheric absorbers such as H(sub2)S, SO(sub2),
S(sub8), and organic hazes. ... ... Cleaves and Miller
(University of California San Diego, US) present an analysis of
the problem and report that even in the absence of atmospheric
shielding there would have been sufficient ultraviolet absorbers
in the ocean to allow for the accumulation of organic material.
These absorbers include organic polymers from electric discharges
and hydrogen cyanide polymerizations, solubilized elemental
sulfur, and inorganics such as Cl(-), Br(-), Mg(2+), SH(-),
Fe(2+). Complete ultraviolet protection could also be provided by
a frozen ocean, an oil slick, or large amounts of organic foams.
The authors suggest that oceanic ultraviolet protectors increase
the size of planetary habitable zones and thereby increase the
number of planets on which life may have arisen.
QY: Stanley L. Miller
(Proc. Natl. Acad. Sci. US 23 Jun 98 95:7260)
(Science-Week 17 Jul 98)
-------------------
Related Background:
BIOCHEMICAL EVOLUTION: POLYMERIZATION ON MINERAL SURFACES
J. Smith (University of Chicago, US) proposes a conceptual
framework for consideration of the origins of replicating
biopolymers. Although extended Darwinian natural selection
coupled with Mendel-Watson-Crick genetic inheritance/mutation
provides a plausible framework for integrating the patchy
paleontological record with the increasingly complex biochemical
zoo of the present Earth, the actual chemical beginning of "life"
still poses major challenges. How could the first replicating and
energy-supplying molecules have been assembled from simpler
materials that were undoubtedly available on the early proto-
continents? Catalysis at mineral surfaces might generate replic-
ating biopolymers from simple chemicals supplied by meteorites,
volcanic gases, and photochemical gas reactions. But many ideas
are implausible in detail because the proposed mineral surfaces
strongly prefer water and other ionic species to organic ones.
The molecular sieve silicalite (Union Carbide; = Al-free Mobil
ZSM-5 zeolite) has a 3-dimensional 10-ring channel system whose
electrically neutral silicon-oxide surface strongly adsorbs
organic species over water, and the ZSM-5 type zeolite mutinaite
has recently been found in Antarctica. The author proposes that
zeolites with similar structures may have existed on the surface
of Earth during its life-origin phase, and that polymer migration
along weathered silicic surfaces of micrometer-wide channels of
feldspars might have led to assembly of replicating catalytic
biomolecules and perhaps primitive cellular organisms. The author
suggests that weakly metamorphosed Archaean rocks might retain
microscopic clues to the proposed mineral adsorbent/catalysts,
and that other frameworks are also possible, including ones with
laevo/dextro one-dimensional channels.
QY: Joseph V. Smith (smith@geol.uchicago.edu)
(Proc. Natl. Acad. Sci. US 31 Mar 98 95:3370)
(Science-Week 8 May 98)
-------------------
Related Background:
ORIGIN OF LIFE: THE PRESENT STATUS OF CHEMICAL THEORY
The essential question involved in the origin of what we call
life is how can order arise from disorder? At the present time,
this question is approached on two fronts: 1) study of the
principal features of self-organizing systems, systems in which
order does arise from disorder, systems in which order is indeed
demanded from disorder on thermodynamic grounds; and 2) study of
the detailed chemistry of such systems, the chemistry of
organization and the chemistry of components. In the case of
components, it is essential that appropriate self-organizing
components exist in the first place if they are to become self-
organized, and such candidate components are thus the focus of
much chemical research in this area. In 1953, the chemist Stanley
Miller reported what soon became a famous experiment. To water
under a gas mixture of methane, ammonia, and hydrogen, he added
an electrical discharge. After one week of continuous electrical
discharge, he found that a number of important biological
molecules, including amino acids, had been formed. Miller
proposed his experiment as a model for the conditions under which
the essential compounds necessary for life originated . The
Miller experiment was a watershed, and it began a new era of
experimentation and analysis of possible primordial components.
Coupled with this, were the new important discoveries by
astrophysicists of the presence of organic molecules in the
interstellar medium and in meteorites. In a review of origin of
life theories, P. Radetsky (Univ. of California Santa Cruz, US)
points out that the Miller theory is no longer the consensus
theory, that contemporary geologists believe the primordial
atmosphere consisted primarily of carbon dioxide and nitrogen,
which are less reactive than the gases in the Miller experiment,
and that the field is currently embroiled in controversy fueled
for the most part by an absence of hard fact. QY: Peter Radetsky,
Univ. of California Santa Cruz 408-429-4008 (Earth February
1988)
(Science-Week 2 Jan 98)
-------------------
Related Background:
RNA POLYMERIZATION A FOCUS AT ORIGIN OF LIFE MEETING
If the complex molecules necessary for life originated on Earth
rather than elsewhere, then a natural question is how? How and
under what conditions did the first polymerizations occur? Under
ordinary laboratory conditions, without special outside agencies
such as catalysts, RNA monomers, for example, will not assemble
into polymers unless the monomer concentration is impossibly
large. So how was polymerization achieved on the early Earth?
Such questions are now the essential questions in the origin-of-
life branch of biological science, and at a recent regional
meeting of the American Chemical Society, a group of researchers
in this area presented results of their latest studies. David
Usher et al have used a "day-night machine", an apparatus that
exposes solutions to alternating cycles of daylight and darkness,
and have apparently found evidence of RNA polymerization from
monomers, the polymerization dependent on the alternating cooling
and heating produced by the light-dark cycles. James Ferris and
Gozen Ertem (Rensselaer Polytechnic Institute, NY US) presented
evidence that clay or pyrite minerals can catalyze polymer
formation from RNA monomers by serving as adsorption templates.
And Tom Waddell et al (University of Tennessee Chattanooga, US)
reported that if intermediates of the citric acid cycle, so vital
in biological processes, are exposed to sunlight, the production
of other intermediates in the cycle is catalyzed. The hunt for
efficient catalysts for RNA polymerization that may have been
present on primeval Earth continues.
(Science 22 Aug 97) (Science-Week 5 Sep 97)
7. MOLECULAR BIOLOGY: AN INTEGRATED TRANSCRIPTION COMPLEX MODEL
In molecular biology, transcription is the process by which
genetic information in DNA is converted into RNA. The central
event in transcription is the *RNA-polymerase-catalyzed
conversion of the sequence code of the template strand of a gene
into a complementary RNA transcript. This RNA may in turn be
translated into a protein, or the RNA may instead serve a
structural or regulatory role, or the RNA may form the genome of
an *RNA virus. Formation of an RNA transcript has traditionally
been divided into 3 sequential stages, called *initiation,
*elongation, and *termination, and all are subject to regulatory
control. ... ... In a review of transcription, Peter H. von
Hippel (University of Oregon, US) presents what is termed "an
integrated model of the transcription complex", and the author
makes the following points: 1) Recent findings now allow the
development of an integrated model of the thermodynamic, kinetic,
and structural properties of the transcription complex in the
elongation, termination, and editing phases of transcript
formation. 2) Concerning the 3 traditional sequential stages, it
may now be more appropriate to divide the overall process into
two major phases: a) activation and transcript initiation, and b)
transcript elongation, with the latter including termination
(transcript release) and editing (transcript shortening and
resynthesis with increased fidelity. 3) The author suggests the
new model provides an operational framework for placing known
facts and can be extended and modified to incorporate new
advances. 4) The most complete information about transcriptional
mechanisms and their control continues to come from the bacterium
Escherichia coli system, upon which most of the explicit
descriptions in the author's model are based. The transcription
machinery of higher organisms, despite its greater inherent
complexity, appears to use many of the same general principles,
and thus the lessons of E. coli continue to be relevant. In
conclusion, the author points out the following problems in
current research in this area: 1) We do not yet know the
molecular structure of any multi-subunit RNA polymerase. 2) We do
not know the exact path taken through the polymerase by the DNA
and RNA framework of the transcription complex. 3) We do not know
how various *transcription factors change the rates of movement
or the stability properties of the transcription complex. 3) We
do not know how these changes are further modulated by the local
sequences of the template and nontemplate DNA and the nascent
transcript.
QY: Peter H. von Hippel
(Science 31 Jul 98 281:660) (Science-Week 28 Aug 98)
-------------------
Related Background:
... ... *RNA polymerase: RNA polymerase is an enzyme that
polymerizes ribonucleoside triphosphates into RNA in the order
dictated by a DNA or RNA template. RNA polymerases are found in
all living cells, with one type found in prokaryotes (cells
without a cell nucleus and other membrane-bound organelles), and
3 types found in eukaryotes (cells with a cell nucleus).
... ... *RNA virus: Viruses either have an RNA genome or a DNA
genome, with the respective nucleic acid core single stranded or
double stranded, depending on the viral species. In general, RNA
viruses are subdivided into 3 types, depending on the details of
the virus-host cell viral replication process.
... ... *initiation: In this context, this is the stage that
begins when RNA polymerase binds to the double-stranded DNA
molecule and incorporates the first nucleotide(s).
... ... *elongation: In this context, the phase during which the
RNA polymerase moves along the DNA template and extends the
growing RNA chain by adding one nucleotide at a time.
... ... *termination: In this context, the stage in which RNA
synthesis ends and the RNA polymerase complex disassembles from
the transcription unit.
... ... *transcription factors: Regulatory proteins that
determine the efficiency with which RNA polymerases bind to DNA
promoter regions during transcription. A "promoter" is a type of
control element, approximately 100 bases long, found in the
genome associated with various genes.
-------------------
Related Background:
MECHANISM OF RNA POLYMERASE NUCLEOSOME TRANSCRIPTION
... RNA polymerase type III is specific to transfer RNA (tRNA)
and ribosomal RNA (rRNA). Transfer RNA is a class of small RNA
molecules that transfer individual amino acids to a growing
polypeptide chain during protein synthesis, and ribosomal RNA is
a class of RNA molecules that have an important role in the
structure of ribosomes, the large molecular entities that carry
out protein synthesis in all cells. All the RNA polymerases are
large and complex molecules with molecular weights of approx-
imately 500,000 daltons. Nucleosomes are higher order structures
of eukaryotic chromosomal DNA, the structures composed of coils
of the DNA double helix around a complex of 8 small basic
proteins called histones. Studitsky et al (4 authors at 2 instal-
lations, US) report that the large yeast RNA polymerase III
transcribes through a single nucleosome, with direct internal
nucleosome transfer in which histones never leave the DNA
template. The authors suggest their results show that a eukary-
otic polymerase is capable of transcribing through a nucleosome
without displacing it from the template, and that this ability
may reflect a property of importance for the transcription
process in vivo.
QY: Gary Felsenfeld, US Nat. Inst. of Health, Bethesda, MD
20892-0148.
(Science 12 Dec 97) (Science-Week 2 Jan 98)
8. ON THE PERMIAN EXTINCTION AND THE GREENHOUSE EFFECT
In geology and paleontology, a "period" is a major subdivision of
an era of geological time distinguished by a particular system of
rocks and associated fossils. The Permian Period is the most
recent period of the Paleozoic Era, and occurred approximately
225 to 270 million years ago. The Permian was characterized by an
abundance of vertebrate and invertebrate forms, a proliferation
of reptilian forms, and a variety of vegetation forms. The
arrangement of the continents was apparently quite different than
at present, with a closer packing of land masses, and the
southern end of Africa well below the Antarctic circle. One of
the more interesting features of the Permian Period is that it
was apparently terminated by a mass biotic extinction of enormous
proportions. ... ... Peter D. Ward (University of Washington
Seattle, US), reviewing the Permian extinction and a current
model to explain it, makes the following points: 1) The Permian
extinction was the greatest mass extinction in Earth's history,
involving the extinction of 90 percent of the species in the
ocean and 70 percent of the species on land. Despite its scale,
the Permian extinction remains a deep mystery. 2) In the fossils
of the past 530 million years, there is evidence of many mass
extinctions, but evidence only of 5 extinctions that killed more
than half the extant species. The best known extinction is the
Cretaceous-Tertiary (also called K/T) event of 65 million years
ago, apparently caused by the impact of a comet or an asteroid,
the event characterized by the extinction of the dinosaurs. But
the K/T event destroyed only about 50 percent of the species on
Earth, which means it was a much less extensive extinction than
the Permian. 3) Knoll et al, in 1995, proposed that the Permian
extinction in the oceans was essentially caused by the release in
the ocean, due to movements of land masses, of carbon dioxide
trapped in sediments, and that it was ocean carbon dioxide, known
to be highly toxic to marine life, that was responsible for the
ocean mass biotic extinction. 4) In the current article, Ward
suggests that ocean carbon dioxide and volcanic gases, both
emerging into the atmosphere, resulted in a heating of the
atmosphere to critical levels. Ward proposes that the surge in
temperature is reflected in the common redness of rock strata
associated with the end of the Permian, the red color a result of
the rusting of iron compounds, and suggesting a climate change of
massive proportions. 5) The author suggests that the Permian
extinction now appears to be a new type of mass extinction,
unrelated to extraterrestrial causes, and occurring much faster
than typical extinctions triggered by internal changes to the
climate and chemistry of the Earth. The author concludes: "Are we
walking down the same path that killed off so much life 250
million years ago -- not from carbon dioxide liberated from the
oceans but from carbon dioxide liberated from our cars and
industry?"
QY: Peter D. Ward, Univ. of Washington Seattle 206-543-8992.
(Discover August 1998) (Science-Week 28 Aug 98)
9. ALZHEIMER'S DISEASE: INTERHEMISPHERIC DISCONNECTION SYNDROME
The term "dementia" refers to a structurally caused permanent or
progressive decline in several dimensions of intellectual
function, the decline interfering substantially with the
individual's normal social or economic activity. There are
various forms of dementia produced by various causes. Alzheimer-
type dementia (Alzheimer's disease) is due to what appear to be
specific cellular and histological degenerative processes, with
loss of cells from the *basal forebrain, cerebral cortex, and
other brain areas, and the brain showing moderate to marked
atrophy. Memory loss is the most prominent early symptom.
... ... Lakmache et al (5 authors at 3 installations, CA) now
report evidence indicating that patients diagnosed as possessing
Alzheimer's disease show deficits in interhemispheric integration
of information, probably reflecting a *corpus callosum
dysfunction. The study involved 10 Alzheimer's disease patients
and 10 matched controls. Patients were given a battery of motor,
somatosensory, and visual tests that required use of either one
or both cerebral hemispheres. Tasks were chosen such that
subjects with Alzheimer's disease performed normally when using
intrahemispheric processing. The same subjects, however,
performed poorly when interhemispheric communication was
required. The authors suggest their observations indicate the
presence of a "disconnection syndrome", and that these
interhemispheric tasks can serve as diagnostic tools for the
early assessment of Alzheimer-type dementia.
QY: Yamina Lakmache, University of Montreal (Psychologie),
C.P.6128, Succursale Centre-Ville, Montreal PQ, H3C 3J7 CA.
(Proc. Natl. Acad. Sci. US 21 Jul 98 95:9042)
(Science-Week 28 Aug 98)
-------------------
Related Background:
... ... *basal forebrain: The forebrain (prosencephalon,
proencephalon) is the largest major division of the human brain,
and apparently associated with the highest intellectual
functions.
... ... *corpus callosum: The large band of nerve fibers that
serves as the primary connection between the two halves of the
brain (see background material below).
-------------------
Related Background:
HUMAN NEUROBIOLOGY: SPLIT-BRAIN RESEARCH
The human nervous system (and the nervous systems of many other
vertebrate species) has a bilateral symmetry most noticeable in
the existence of the two cerebral hemispheres. The two halves of
the brain, although exhibiting certain functional specializat-
ions, ordinarily work in an integrated manner to produce the
conscious output of the nervous system, namely thought and
action. Epilepsy is the general name given to a class of nervous
system disorders involving convulsive activity of large numbers
of nerve cells, and a classical surgical procedure in cases of
severe epilepsy is section of the corpus callosum, the large band
of nerve fibers that serves as the primary connection between the
two halves of the brain. More than 30 years ago, Roger W. Sperry
(1913-1994) and his coworkers began a series of studies of
"split-brain" humans, patients who had had the corpus callosum
severed as a therapeutic procedure, and the observations of these
clinical patients have formed the basis for a number of signif-
icant ideas concerning brain function. ... ... Michael S.
Gazzaniga (Dartmouth College, US), a member of Sperry's original
group, presents a review of the history and current status of
human split-brain research, and makes the following points: 1) In
the classical split-brain patient, visual information no longer
moves between the two sides of the brain. If an image is
projected to the right visual field (i.e., to the left
hemisphere, which is where information to the right field is
processed) patients can describe what they see. But when the same
image is displayed to the left visual field (i.e., to the right
hemisphere), the patient cannot describe what they see. But if
the patient is asked to point to an object similar to the object
being projected, they do so with ease. The right brain sees the
image and can mobilize a nonverbal response, but it cannot talk
about what it sees. 2) The same situation obtains for touch,
smell, and sound. 3) Additionally, each half of the brain can
control the upper muscles of both arms, but the muscles
manipulating hand and finger movements can be orchestrated only
by the contralateral hemisphere. In other words, the right
hemisphere can control only the left hand and the left hemisphere
only the right hand. 4) Ultimately, it was discovered that the
two hemispheres control vastly different aspects of thought and
action. Each half of the brain has its own specialization, and
thus its own limitations and advantages. The left brain is
dominant for language and speech, the right brain excels at
visual-motor tasks. 5) During the past decades, research in
cognitive science, artificial intelligence, evolutionary
psychology, and neuroscience has directed attention to the idea
that brain and mind are built from discrete units -- or modules -
- that carry out specific functions. According to this theory,
the brain is not a general problem-solving device whose every
part is capable of any function. Rather it is a collection of
devices that assists the mind's information processing demands.
Gazzaniga concludes: "After many years of fascinating research on
the split brain, it appears that the inventive and interpreting
left hemisphere has a conscious experience very different from
that of the truthful, literal right brain. Although both
hemispheres can be viewed as conscious, the left brain's
consciousness far surpasses that of the right. Which raises
another set of questions that should keep us busy for the next 30
years or so."
QY: Michael S. Gazzaniga, Dartmouth College 603-646-2875.
(Scientific American July 1998) (Science-Week 10 Jul 98)
-------------------
Related Background:
ON MODULAR COGNITIVE SYSTEMS IN THE HUMAN BRAIN
One of the central challenges of cognitive neuroscience is to
unmask the apparent unitary nature of perceptual, memorial, and
cognitive systems. Neuropsychological analyses, functional brain-
imaging methods, and analyses of normal reaction times have
revealed that apparently unitary processes consist of multiple
components. Frequently, these multiple components are distributed
across the cerebral hemispheres, but appear unified because of
the integration possible via the corpus callosum.
... ... Baynes et al (4 authors at 3 installations, US) report a
case of elective surgery for a severe epileptic disorder, the
surgery involving a resection of the corpus callosum in a left-
handed woman with left-hemisphere dominance for spoken language.
The patient demonstrated a dissociation between spoken and
written language. Words flashed to the dominant left hemisphere
were easily spoken out loud, but could not be written. When words
were flashed to the patient's right hemisphere, she could not
speak them out loud but she could write them with her left hand.
The authors suggest this marked dissociation supports the view
that spoken and written language output can be controlled by
independent hemispheres, even if before hemispheric disconnection
spoken and written language appear as inseparable cognitive
entities.
QY: Kathleen Baynes
(Science 8 May 98 280:902) (Science-Week 29 May 98)
10. KAPOSI'S SARCOMA: FURTHER EVIDENCE FOR ROLE OF HERPESVIRUS
Kaposi's sarcoma is an ordinarily rare cancer that can be common
in humans with compromised immune systems (for example, in AIDS).
Kaposi's sarcoma-associated herpesvirus (KSHV) (also called
"human herpesvirus 8") is invariably present in Kaposi's sarcoma
lesions. KSHV contains several viral *oncogenes, and there is
evidence that KSHV infection is necessary for the development of
Kaposi's sarcoma. However, cellular transformations by this virus
have not so far been demonstrated. In Kaposi's sarcoma lesions,
the virus has been found in *endothelial cells and cells of
endothelial origin. ... ... Flore et al (6 authors at 3
installations, US IT IE) report an investigation of the
biological consequences of infecting cultured human primary
endothelial cells with purified KSHV particles. The authors
report that infection causes long-term proliferation and survival
of these cells, the effects associated with the acquisition of
*telomerase activity and *anchorage-independent growth. KSHV was
present in only a subset of cells, with *paracrine mechanisms
responsible for the survival of uninfected cells, perhaps by
*upregulation of a receptor for vascular endothelial growth
factor. The authors suggest their results indicate that
transformation of endothelial cells by KSHV, as well as paracrine
mechanisms that are induced by this virus, may be critical in
the pathogenesis of Kaposi's sarcoma.
QY: Ethel Cesarman
(Nature 6 Aug 98 394:588) (Science-Week 28 Aug 98)
-------------------
Related Background:
... ... *oncogenes: There are two general meanings of this term
in current use. The first meaning refers to any of a family of
cellular genes that normally code for proteins involved in cell
growth or regulation, but which may produce malignant processes
when mutated or activated by viruses. The second meaning of the
term "oncogene" refers to viral genes found in certain DNA tumor
viruses, genes that are required for viral replication, but whose
activation produces malignant transformations.
... ... *endothelial cells: Flat cells forming a layer lining
blood vessels, lymphatic vessels, the heart, etc.
... ... *telomerase: Telomeres are defined ends of chromosomes
that contain specific repeated DNA sequences. They are essential
for normal chromosome replication, and since their length
shortens a bit with each replication, they are believed to be
involved in the aging of the cell. Telomerase is an enzyme that
repairs damage to telomeres, and it is thought by some that
cancerous cells may have mutant telomerase, the mutant enzyme
conferring immortality on the cancer cell.
... ... *anchorage-independent growth: In multicellular
organisms, cells are specialized to be either free-floating
(e.g., blood cells) or anchored to the extracellular matrix
(e.g., cells forming the tissues of organs). Anchored cells are
known to require their anchorage: if the anchorage is lost, the
cells normally undergo apoptosis (programmed cell death).
Malignant cells, however, have lost both anchorage dependence and
the consequent apoptosis.
... ... *paracrine mechanisms: These are localized chemical
regulatory mechanisms -- as opposed to hormonal mechanisms,
which are systemic rather than localized.
... ... *upregulation: An increase in the number of receptor
molecules present within the plasma membrane.
-------------------
Related Background:
FURTHER EVIDENCE OF HERPES VIRUS ROLE IN KAPOSI'S SARCOMA
Kaposi's sarcoma is a human cancer of skin cells (and sometimes
cells of certain internal tissues), appearing for the most part
in elderly men or in younger men with compromised immune systems.
The disease was first described by the Hungarian dermatologist
Moritz Kaposi (1837-1902). ... ... Martin et al (6 authors at 3
installations, US) report a study of human herpes virus type 8
(HHV-8). The prevalence of HHV-8 infection is high among
homosexual men, correlates with the number of homosexual
partners, and is temporally and independently associated with
Kaposi's sarcoma. The authors suggest their observations are
further evidence that HHV-8 has an etiological role in Kaposi's
sarcoma and is sexually transmitted among men, and that
understanding the epidemiology of HHV-8 is a critical first step
in designing interventions to decrease the transmission of this
pathogen.
QY: Dean H. Kedes, Univ. of Calif. San Francisco 415-476-4044.
(New England J. Med. 2 Apr 98) (Science-Week 10 Apr 98)
-------------------
Related Background:
HERPES VIRUS AS A VIRAL ONCOGENE AND ANGIOGENESIS ACTIVATOR
Kaposi's sarcoma is an ordinarily rare cancer that can be common
in humans with compromised immune systems (for example, in AIDS),
and the herpes viruses are a class of viruses producing the
complex of herpes diseases, some of which are sexually transmit-
ted diseases clinically associated with AIDS. In cell biology,
the term "receptor" denotes a cell surface chemical entity,
usually a protein, that interacts with messenger molecules (e.g.,
hormones) in the extracellular solution. G-proteins are a family
of signal-coupling proteins that act as intermediaries between
activated cell receptors and effectors, for example, the trans-
duction of hormonal signals from the cell surface to the cell
interior. The G-protein is apparently embedded in the cell
membrane with parts exposed on the outside surface and inside
surface. The outside moiety is activated by the first messenger,
and the inside moiety activates the second messenger (which
begins a cascade of signals in the interior of the cell), the G-
protein thus acting as a trans-membrane signal transducer. In the
context of this report, the term "transformation" refers to the
conversion of normal cells into malignant cells exhibiting
uncontrolled growth and loss of functional specialization
(dedifferentiation). Angiogenesis, the origin and development of
blood vessels, is an important consideration in the growth of
cancerous tumors, since the tumor provokes directed angiogenesis
into itself with the end result that the tumor is supplied with
oxygen and nutrients. Without angiogenesis, tumors can attain
only a small size before becoming self-inhibiting. A cytokine is
any substance that promotes cell growth and cell division, and an
inflammatory cytokine is a cytokine involved in the inflammatory
response to tissue injury and infection. As a promoter of cell
growth and division, a cytokine acts as a messenger to cells, and
the transmission of the message requires a binding of the
cytokine molecule to a cytokine-specific receptor on the cell
surface. This receptor is either a protein or a protein complex
or a part of a protein. The lymphatic system is a complex network
for the distribution of lymph fluid (which is similar to blood
plasma -- blood without red cells), and lymphoma is a general
term for a tumor (benign or malignant) of tissue of the lymphatic
system. Bais et al (10 authors at 2 installations, US) report
that signaling by the Kaposi's sarcoma-associated herpes virus G-
protein-coupled receptor leads to cell transformation and tumor
growth, and activates angiogenesis by mechanisms similar to those
produced by inflammatory cytokines. The authors suggest this is
the first demonstration that a Kaposi's sarcoma-associated
herpes virus gene is capable of inducing both transformation and
angiogenesis, and that this evidence strongly supports the idea
that Kaposi's sarcoma-associated herpes virus infection plays a
direct role in Kaposi's sarcoma pathogenesis and lymphoma-
genesis. QY: Enrique A. Mesri
(Nature 1 Jan 98)
-------------------
Related Background:
VIRUSES IN NORMAL CELLS MAY DRIVE GROWTH OF TUMOR CELLS
The idea that viruses are implicated in cancer has existed for
decades, and indeed in a few types of malignancy a related virus
has been identified. But the thinking has always been that if a
virus is implicated in cancer, it is because it invades a cell
type, corrupts the cell's genetic machinery, and the result is a
wild cell that rapidly proliferates. Now a new scheme has
appeared, reported by M. B. Rettig et al (various installations
in Los Angeles, including the University of California Los
Angeles; US). What they have found is that in cases of the human
cancer multiple myeloma, healthy neighboring dendritic cells in
human bone marrow are infected with Kaposi sarcoma-associated
herpes virus, and that this virus is orchestrating the production
by these healthy cells of interleukin-6, a protein which is known
to stimulate myeloma growth. What is striking, is that the virus
does not infect the malignant cells. If these results are
independently confirmed, there will be an intense new interest in
the possibility of viral promotion of various human malignancies.
(Science 20 Jun 97)
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