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.

September 10, 1999 -- Vol. 3 Number 37

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I believe there is no philosophical high-road in science,
with epistemological signposts. No, we are in a jungle
and find our way by trial and error, building our road
behind us as we proceed.
-- Max Born (1882-1970)

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Contents of This Issue:

1. Astrophysics: Black Holes as Empirical Objects
2. On Paleontology and Evolutionary Biology
3. On the Origin of RNA
4. Bacteria: Chaperones and Protein Assemblies
5. Tumor Viruses and Oncogenes
6. On Estrogen and the Cardiovascular System

In Focus: On Physical Optics and Early 20th Century Physics

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1. ASTROPHYSICS: BLACK HOLES AS EMPIRICAL OBJECTS
During the life of a star, two opposing forces control the
star's equilibrium: the gravitational force, which drives the
collapse of the star's mass inward to the center of gravity, and
the counteracting outward pressure derived from the nuclear
fusion reactions in the star's core. When the nuclear fuel burns
out, the star begins its death and gravitational collapse
occurs. If the terminal stages of star death (during which large
amounts of stellar material are blown away) leave a remnant star
mass greater than 3 solar masses, the ultimate gravitational
collapse will produce a black hole, a relativistic singularity.
A black hole is a localized region of space from which neither
matter nor radiation can escape. The "trapping" occurs because
the requisite escape velocity, which can be calculated from the
relevant equations, exceeds the velocity of light and is
therefore unattainable. Another view of a black hole is that it
is a mass that has collapsed to such a small volume that its
gravity prevents the escape of all radiation. Space and time
essentially have no meaning in a black hole. The boundary of the
black hole is called the "event horizon", because any event
within the boundary is invisible outside, the invisibility
resulting from the fact that no radiation can escape to be
detected. The radius of the black hole depends upon how much
matter has fallen into the region; it is called the
"Schwarzchild radius", and it is usually a few kilometers.
However, massive black holes are possible and are thought to be
the source of quasars (quasi-stellar objects), which are
extremely luminous sources radiating energy over the entire
spectrum from x-rays to radio waves, and which are apparently
the oldest and most distant objects in the universe. If quasars
indeed involve black holes, the radiation is from material just
outside the black hole, and not from anything within it. Nothing
inside a black hole can get out of it. Other massive black
holes, closer to us than quasars, are apparently the centers of
galaxies, both *galaxies with active centers and galaxies with
dormant centers.
... ... R.Blandford and N. Gehrels (2 installations, US) present
a review of current research on black holes, with a focus on
observable phenomena. The authors make the following points:
     1) The term "black hole" was introduced in a lecture by John
Wheeler in 1968, and used to describe a new view of gravitational
collapse, a shift in perspective from that of an observer at
infinity, for whom the black hole is a limiting case and never
forms, to a description of a black hole in terms of the fate of
matter falling into it as the matter crosses the event horizon.
     2) Energy is the key to understanding astrophysical black
holes. For the past three decades, it has become well established
theoretically that black holes can be voracious monsters
devouring all that they encounter. Some black holes are extremely
luminous and easily outshine their stellar and galactic
counterparts that rely on nuclear, as opposed to gravitational,
energy for their power. Since the late 1970s, it has been well
understood that black holes are most likely to be detected in
stellar *binary systems of approximately 10 solar-masses (i.e.,
10 times the mass of the Sun, whose mass is approximately 2 x
10^(30) kilograms), and in galactic nuclei with masses of the
order of 10^(6) to 10^(9) solar masses.
     3) The archetype of the stellar black hole is Cygnus X-1, a
powerful x-ray source varying so rapidly that it must be a
compact star. Only 3 types of compact stars are known: *white
dwarfs, *neutron stars, and black holes. But theory indicates
that of compact stars only black holes can have masses greater
than 3 solar-masses. Since application of Kepler's laws to Cygnus
X-1 in 1971 resulted in an estimated mass of 8 solar-masses, this
object was established as a black hole.
     4) For black holes in active galactic nuclei, dynamical
investigations beginning in the late 1970s, established that
galaxies, such as the giant *elliptical galaxy M87 in the Virgo
Cluster, contain central dark masses (3 x 10^(9) solar-masses in
the case of M87) that appeared to be too compact to be a central
cluster of stars. In 1995, M. Miyoshi et al were able to measure
the orbital speed of the gaseous disk around the nucleus of the
nearby spiral galaxy NGC 4258. The authors demonstrated that the
gas speed obeys Kepler's laws, and that the gaseous disk is
warped. Since the calculated mass and size of the central object
are 4 x 10^(7) solar-masses and half a light year, respectively,
the consensus is that the central object is definitely a black
hole.
     5) Concerning our own Galaxy, measurements of motions and
velocities of individual stars in orbit around the center of the
Galaxy indicate the mass of our own black hole has a value of 2.6
x 10^(6) solar-masses.
     6) The authors suggest that at the present time we have 15
mass estimates for black holes in the nuclei of nearby galaxies
that are quite secure. It appears that the majority of nearby
luminous galaxies now contain dormant black holes. However,
during earlier epochs, when the black holes were supplied with
gaseous fuel at a much higher rate, they were able to outshine
their host galaxies, in some cases by factors of thousands. These
ancient objects are the quasars, which we can spot from distances
so large that many of them emitted the light we see now when the
Universe was less than 10 percent of its present age.
     7) In summary, the authors note: "The past five years have
seen a remarkable gain in the sophistication of black hole
observations with telescopes that span the entire electromagnetic
spectrum. No longer is there any serious debate as to whether
black holes exist. We know that they must be quite common, and we
can now study them in increasing detail."
-----------
R. Blandford and N. Gehrels: Revisiting the black hole.
(Physics Today June 1999)
QY: Roger Blandford, Calif. Institute of Technology 818-395-6811.
-----------
Text Notes:
... ... *galaxies with active centers: Active galactic nuclei are
central regions of galaxies in which considerable energy is
apparently generated by processes other than those operating in
ordinary stars. The energy may result from the accretion of
material into a massive black hole situated at the core of the
galaxy.
... ... *binary systems: Binary stars are a pair of stars
revolving around a common center of mass under the influence of
their mutual gravitational attraction, and apparently the
majority of stars in the universe are binaries and not singlets.
In some cases the binary system is resolvable into two
components, and in other cases the presence of a second star is
inferred by perturbations in the motion or emitted radiation of
the first star. If the binaries are close enough, they may share
stellar material, and this results in a particular kind of
stellar evolution.
... ... *white dwarfs: White dwarf stars are extremely dense
and compact stars that have undergone gravitational collapse.
They are the final stage in the evolution of low-mass stars after
they have lost their outer layers. White dwarf stars are
approximately the size of Earth, but with a mass approximately
that of the Sun.
... ... *neutron stars: If, following its terminal stages, the
remnant mass of a star is between 1.4 and 2 to 3 solar masses,
the star will collapse into a neutron star, a body with a radius
of 10 to 15 kilometers, with a core so dense that its component
protons and electrons have merged into neutrons.
... ... *elliptical galaxy: In 1925, the astronomer Edwin Hubble
introduced a classification scheme for galaxies that is now
widely used. The scheme has 3 main types of galaxy: elliptical,
spiral, and barred spiral, and each is further divided into
morphological subtypes. Elliptical galaxies are apparently
composed of old stars, contain little dust, are the central
dominant galaxies in rich clusters, and many are powerful sources
of radio wavelength radiation. The size of elliptic galaxies
ranges from dwarf ellipticals [10^(8) stars] to supergiant
ellipticals [10^(13) stars]. Elliptical galaxies are believed to
be a stage in the evolution of galaxies, and different
cosmological models make specific predictions about the number of
elliptical galaxies as a function of redshift. In principle,
therefore, observations of elliptical galaxies can be used to
discriminate between models.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 10Sep99
-------------------
Related Background:
ON THE EXISTENCE OF BLACK HOLES
... ... Jean-Pierre Lasota (Institute of Astrophysics Paris, FR)
presents a review of current studies of apparent black holes and
the evidence for the existence of black holes, the author making
the following points:
     1) To deduce the existence of black holes, astrophysicists
have had to rely on two indirect lines of argument. a) Near
galactic centers, stars are moving so rapidly that they would fly
off unless the gravity of a huge mass -- as large as the
equivalent of a billion Suns -- held them in. Whatever has this
mass must be extremely dense, and there is no known theoretical
alternative to a black hole. b) Many galactic centers and binary
star systems spew radiation and matter at enormous rates, which
suggests they contain an extraordinarily efficient mechanism for
generating energy. Again, in theory, the most efficient engine
possible is a black hole.
     2) The above lines of argument, however, are indirect, a
deduction by default: Such evidence indicates only the existence
of some kind of compact body, but it does not positively identify
black holes based on any of the unique characteristics of black
holes.
     3) A central problem in the study of black holes has been to
discover how to distinguish them from neutron stars. In recent
years, a method has been developed, a method based on x-ray
emissions from the vicinity of each type of body. This method has
allowed the demonstration that black holes are indeed a reality.
The x-ray emissions of x-ray binary systems have been
particularly revealing.
     4) The inferred temperature of the collapsed entity in
certain x-ray binary systems is of the order of 10^(7) degrees
kelvin, which is consistent with that expected for a black hole.
To generate the observed emission, a black hole would need to
swallow 10^(-9) to 10^(-8) solar mass per year -- which agrees
with estimates of how quickly the ordinary star in the binary
system is losing mass to its companion. Thus, certain x-ray
binaries could be the best proof that stellar-mass black holes
exist.
     5) It is known, however, that in many cases the compact
object in the binary systems is not a black hole. Radio pulsars
found in binaries are thought to be rapidly rotating magnetized
neutron stars. Astronomical black holes cannot have magnetic
fields. They are nearly featureless objects and cannot generate
the regular pulses observed in pulsars. Similarly, x-ray pulsars
cannot be black holes. Any regular stable pulsation rules out the
presence of a black hole. Even irregular x-ray bursts entail a
neutron star, which provides a surface on which matter can
accumulate and explode.
     6) Recently, evidence for the existence of black holes has
come from comparison of the brightness of objects exceeding 3
solar-mass with that of objects of less than 3 solar-mass. The
more massive objects are fainter than the less massive objects,
even under conditions where radiation should be emitted at the
same rate. The discrepancy can be explained if matter and energy
are disappearing, which only a black hole could accomplish.
     7) The theoretical modeling of flows into black holes is an
active field of research. Bodies too massive to be neutron stars
can now be moved from the category of black hole candidate to
confirmed black hole. Only an object with an event horizon can
cause energy to disappear in the manner that is inferred for
certain x-ray binary systems.
-----------
Jean-Pierre Lasota: Unmasking black holes.
(Scientific American May 1999)
QY: Jean-Pierre Lasota, Institute of Astrophysics, Paris FR.
-----------
Text Notes:
... ... *Schwarzchild radius: Named after the astronomer Karl
Schwarzchild (1873-1916). In 1916, he demonstrated that in the
general theory of relativity, a sphere of material approximating
to a star, collapsing under its own gravitational field to less
than a certain radius, would cease to radiate energy. The term
"black hole" was apparently first applied to such an object by
John Archibald Wheeler many years later (1968). The Schwarzchild
calculation yielded what is called a "Schwarzchild black hole",
which is a black hole without charge and without angular
momentum. The current consensus is that real black holes have
little or no charge but are almost certainly rotating, and these
black holes are called "Kerr black holes".
... ... *Chandrasekhar limit: Named after Subrahmanyan
Chandrasekhar (1910-1995), who presented the first theoretical
derivation of the limit in 1939. The limit actually ranges from
1.11 to 1.44 solar-mass, depending on the composition and
structure of the star.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 18Jun99
-------------------
Related Background:
ON BLACK HOLES
In an essay on black holes, Martin Rees (Cambridge University,
UK) makes the following points: 1) Black holes are expected in
many theories of gravity, not just in Einstein's general
relativity theory. Indeed, black holes were in essence
conjectured more than 200 years ago, when in 1783 John Michell
presented a paper to the Royal Society of London concerning the
effect of gravity on light. 2) But the term "black hole" was not
coined until 1968, when John Wheeler described how an infalling
object "becomes dimmer millisecond by millisecond... light and
particles incident from outside... go down the black hole only to
add to its mass and increase its gravitational attraction." 3)
Viewed from the outside, black holes are exactly standardized
objects -- no traces persist to distinguish how a particular hole
formed or what kind of objects it swallowed. The combined efforts
of several theorists had proved this result by the early 1970s.
4) The paradoxes within a black hole are as fundamental, and as
far-reaching in their implications, as the puzzles that
confronted Einstein's contemporaries at the beginning of the 20th
century and triggered the development of relativity and the
quantum theory. Black holes preclude space and time being a
seamless continuum, and they may be gateways to other space-times
sprouting from our own. The existence of black holes not only
allows, but may even require, a broadening cosmic perspective
that envisions our universe as just a member of an ensemble. 5)
Ad hoc explanations for observed cosmic phenomena that do not
involve black holes can be devised, but they are generally too
contrived to be convincing, and black holes remain the most
plausible endpoints for certain types of stellar evolution. 6)
The evidence for supermassive extra-Galactic black holes is now
even more compelling than for black holes within our own galaxy.
In the centers of some galaxies, gas and stars are evidently
swirling into a black hole weighing as much as millions or even
billions of Suns. They manifest themselves as quasars or as
intense sources of cosmic radio emission. These supermassive
black holes have diameters as large as our solar system. 7) Rees
concludes with a quotation from the astrophysicist Roger Penrose:
"It is ironic that the astrophysical object which is the
strangest and least familiar, the black hole, should be the one
for which our theoretical picture is most complete."
QY: Martin Rees, King's College, Cambridge University, UK.
(Astronomy July 1998) (Science-Week 3 Jul 98)


2. ON PALEONTOLOGY AND EVOLUTIONARY BIOLOGY
Paleontology, the study of the history of life as recorded by
fossil remains, is one of the interfaces between the two fields
of biology and geology. The fossil record includes a diverse
class of objects ranging from molds of microscopic bacteria in
rocks more than 3 billion years old to unaltered bones of human
fossils only a few thousand years old. The quality of
preservations ranges from the occasional occurrence of soft parts
to barely decipherable impressions made by shells in soft mud
that later hardened to rock. Concerned as it is with the physical
record of the history of life, the sister discipline of
paleontology is evolutionary biology.
... ... David Jablonski (University of Chicago, US) presents a
review of the common ground between paleontology and evolutionary
biology, the author making the following points:
     1) The next wave of research in paleontology apparently will
build on an array of empirical and methodological advances that
will foster a paleontology more interdisciplinary than ever.
Among the opportunities opened by new developments, four key
interrelated research questions have emerged at the interface
between paleontology and evolutionary biology:
... ... a) What are the rules that govern biodiversity dynamics,
and do these rules apply at all temporal and spatial scales? The
overall trend of plant and animal biodiversity -- whether
measured in terms of taxa, range of body forms, or modes of life
-- has been one of net increase through geologic time. However,
this general trend has been anything but smooth. Diversification
has occurred episodically, has been interrupted by extinction
events, and has had (e.g., in the oceans) at least one prolonged
episode of little net change.
... ... b) Why are major evolutionary innovations unevenly
distributed in time and space? One of the most striking patterns
to emerge from the fossil record is that biological innovations
-- the breakthroughs that open new ecological opportunities and
evolutionary pathways -- do not arise randomly. Regardless of
when the major lineages actually split, the *Cambrian explosion
represents a uniquely rich and temporally discrete episode of
morphological invention for the *metazoan phyla. Smaller pulses
follow mass extinctions, for example, the exuberant *Cenozoic
radiation of mammals after 100 million years of monotonous
morphologies in the shadow of the dinosaurs.
... ... c) How does the biosphere respond to environmental
perturbations at global and regional scales? Life has been
buffeted by asteroid impacts, rapid climate changes, shifts in
oceanic and atmospheric chemistry, continent-scale biotic
interchanges, and a host of other perturbations. The fossil
record provides the basis for a comparative calibration of biotic
responses to different types and magnitude of disturbance.
... ... d) How have biological systems influenced the physical
and chemical nature of the Earth's surface and vice versa? In the
long and complex path from the anoxic, exclusively microbial
*Archean sea to the highly heterogeneous modern system, the major
biological, sedimentary, and geochemical transitions are roughly
coincident in time. Combining the biological record with
increasingly high resolution geochemical methods, researchers are
beginning to focus on time intervals when significant changes
occurred in biological materials and biogeochemical cycling, on
how steady states are maintained, and on the roles of biological
innovations in perturbing and stabilizing those cycles.
     2) The author concludes: "Paleontology sits squarely at the
interface between the earth and life sciences. The most powerful
contributions will emerge from analysis of evolutionary dynamics
at different scales and hierarchical levels over deep time and of
the diverse ways life has driven, and been driven by, changes
in the Earth's atmosphere, oceans, and lithosphere."
-----------
David Jablonski: The future of the fossil record.
(Science 25 Jun 99 284:2114)
QY: David Jablonski [djablons@midway.uchicago.edu]
-----------
Text Notes:
... ... *Cambrian explosion: The geological period known as the
Cambrian is the time frame from about 505 million years ago to
545 million years ago. Its most outstanding aspect is the rather
sudden appearance of numerous invertebrate fossils, so numerous
that some have termed it an explosion of evolutionary processes.
Many of the life forms that existed during the Cambrian are long
extinct, but their fossils are numerous, and through their
fossils the various Cambrian species have been the subject of
much study by paleobiologists. The Cambrian explosion of life
forms has been a long-standing puzzle for paleobiologists, and at
present there is apparently no single generally accepted
explanation. Among the ideas proposed have been, 1) that the
explosion of new forms resulted from a sudden increase in
atmospheric oxygen; 2) that the explosion is only apparent, and
the Precambrian, the period previous to the Cambrian, lacks
fossils because of heat and pressure associated with important
geological changes; 3) that living forms evolved mostly in
freshwater areas, and are therefore absent in Precambrian
sediments, which are primarily marine; 4) that changes in the
shape and extent of shorelines produced by continental drift
dramatically transformed climate and environment; 5) that the
previous evolution of DNA recombination and regulatory genes
culminated in and sparked the diversity and anatomical complexity
manifested in the explosion; 6) that an exponential increase of
species could become significant only after attaining a threshold
value at the start of the Cambrian; and, 7) that once
multicellular organisms appeared, the intrinsic possibilities for
variation increased enormously with a resultant explosion of
evolved forms. Unfortunately, there is no evidence to suggest a
selection of one of these proposals, although some of them are
less convincing than others. And of course the truth may be that
more than one factor was involved. No matter the origin, the
Cambrian explosion is apparently accepted by most paleobiologists
as a real discontinuity, a period that saw the sudden emergence
of dozens of new orders and phyla, including sponges, *annelids,
*crustaceans, *hemichordates, *brachiopods, and *mollusks. 
... ... *annelids: Soft-bodied, metamerically segmented coelomate
worms, e.g., earthworms. The term "coelomate" refers to the
possession of a body cavity.
... ... *crustaceans: A class of Arthropods, including shrimps,
crabs, water fleas, etc.
... ... *hemichordates: A group of marine invertebrates,
including the acorn worms.
... ... *brachiopods: Bivalve coelomate invertebrates that live
attached to the sea-bed (e.g., lamp shells).
... ... *mollusks: (Mollusca) A phylum of bilaterally symmetrical
unsegmented invertebrates. Includes aquatic bivalves such as
mussels and clams, terrestrial slugs and snails, octupi and
squids.
... ... *metazoan phyla: In general, a "phylum" is any major
group. A "metazoan" is any multi-cellular animal.
... ... *Cenozoic radiation: The Cenozoic is the present geologic
era, extending from about 65 million years ago to the present.
Also called "the age of mammals". In this context, the term
"radiation" refers to the spread of a group of biological
entities into new environments with consequent diversification.
... ... *Archean sea: (Archaean; Archeozoic) In general, the
earliest biotic geological era, from approximately 3.9 billion
years ago to approximately 2.6 billion years ago.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 10Sep99
-------------------
Related Background:
IN FOCUS: ON INVERTEBRATE PALEONTOLOGY
"Little work of importance was done in paleontology until the
1700's, at which time both vertebrate and invertebrate fields
began to assume importance. Intensive work in the invertebrate
area arose from recognition of the fact, first clearly seen by
William Smith, an English civil engineer and amateur geologist of
the period, that a given set of beds tended to contain the same
species of shells over vast and widely separated areas. Accurate
determination of fossils could thus be of great practical use to
the stratigrapher; as a result, invertebrate paleontology tended
to develop not as an independent science, but as a handmaiden to
the geologist -- a working tool for the stratigrapher looking for
oil or ores or coal. The fossil shells were rarely thought of as
the remains of once-living organisms, but merely as convenient
markers for the identification of successive formations, and
would have been as useful had they been identifiable mineral
inclusions or distinctive assortments of nuts and bolts... With
this background, the invertebrate workers of Darwin's day not
merely lacked interest in evolutionary ideas, but were inclined
to view them with suspicion as detrimental to their work. For
clear-cut stratigraphic work, the species in a given formation
should be stable entities, clearly distinguishable from those in
the strata above and below. The idea of gradual change and of
transitional forms was abhorrent... With this to contend with, it
is apparent why Darwin was thrown on the defensive in his
treatment of the fossil record. He could not call on the
paleontologists for support; the most he could do was to attempt
appeasement, to show that it was at least possible to interpret
the geological story in evolutionary terms, and that there was no
insuperable objection."
-----------
-- A.S. Romer: "Darwin and the Fossil Record"
   (in S.A. Barnett [ed.]: _A Century of Darwin_, 1958, Chap. 6)
(Science-Week 25 Jun 99)
-------------------
Related Background:
A MOLECULAR DATING TEST OF THE CAMBRIAN EXPLOSION HYPOTHESIS
The early history of the *Metazoa, whether the Metazoa originated
as part of a *Cambrian "explosion" or with an extended
*Precambrian "phylogenetic fuse", remains controversial in
evolutionary biology. The Cambrian explosion hypothesis -- that
the phyla and even classes of the animal kingdom originated in a
rapid evolutionary radiation at the base of the Cambrian at 545
to 560 million years ago -- rests on the sudden appearance of a
diverse range of animals in the fossil record. Although recent
discoveries of *Ediacaran metazoans have extended the record of
sponges and bilateral animals to 570 million years ago, the
biological affinities of many Ediacaran organisms remains
controversial, and the earliest paleontological evidence of
metazoan life is no more than 600 million years ago. However, the
absence of earlier metazoan fossils could have been caused by
systematic biases in preservation that left the Precambrian
history of recognized phyla unrecorded in fossils. Molecular
studies have the potential to shed light on the origin of the
animal phyla by providing independent estimates of the divergence
times, but molecular studies have been criticized for failing to
account adequately for variations in rate of evolution.
... ... L. Bromham et al now present a study involving a method
of dating divergence times from molecular data (both
*mitochondrial DNA and nuclear DNA) which addresses the
criticisms of earlier studies, and which the authors state
provides more realistic but wider confidence intervals. The
authors report their data are not compatible with the Cambrian
explosion hypothesis as an explanation for the origin of metazoan
phyla, and they suggest their data provide additional support for
an extended period of Precambrian metazoan diversification. The
authors conclude: "Although we cannot provide precise estimates
of the origin of metazoan phyla, we can use our results to
confidently reject the Cambrian explosion hypothesis, which rests
on a literal interpretation of the fossil record and assumes that
special evolutionary phenomena, capable of producing profound
differentiation in a short period, operated in the Cambrian but
not before or since. By contrast, the Precambrian phylogenetic
fuse hypothesis assumes no more than we already know to be
reasonable: that lineages can diverge gradually over time and
that the fossil record contains gaps that can greatly reduce the
chances of finding fossils for certain periods or particular
types of organisms.
-----------
L. Bromham et al (3 installations, UK NZ)
Testing the Cambrian explosion hypothesis by using a molecular
dating technique.
(Proc. Natl. Acad. Sci. US 13 Oct 98 95:12386)
QY: Lindell Bromham [LBromham@zoology.uq.edu.au]
-----------
Text Notes:
... ... *Metazoa: In general, the term "metazoa" refers to all
multicellular animals. Among important distinguishing
characteristics of metazoa are cell differentiation and
intercellular communication. For certain multicellular colonial
entities such as sponges, some biologists prefer the term
"parazoa".
... ... *Cambrian "explosion": See notes in main report above.
... ... *Precambrian "phylogenetic fuse": The term "fuse" here is
a metaphor for a proposed long series of precursor events leading
to the apparent "explosion" in the fossil record. The essential
question is whether the apparent explosion in the fossil record
was the result of relatively sudden changes in preservation
constraints (e.g., hard-body vs. soft-body forms), or whether a
set of special conditions (e.g., climate change or atmospheric
oxygen availability) provoked an actual rapid diversification of
forms.
... ... *Ediacaran metazoans: The term "Ediacaran" refers to an
assemblage (until recently the oldest) of soft-bodied marine
animals, the assemblage first discovered in the Ediacara Hills in
Australia.
... ... *mitochondrial DNA: Mitochondrial DNA (sometimes denoted
as mtDNA), found in the mitochondria of all eukaryotes, is
believed to evolve in parallel with nuclear DNA, but since sperm
lose their mitochondria, it is inherited only in the maternal
lineage in animals.
-------------------
Related Background:
EVOLUTION: 1 BILLION YR OLD FOSSILS OF TRIPLOBLASTIC ANIMALS
There are two contradictory views concerning the early history of
*metazoans. The "*Cambrian explosion" hypothesis is based on
Cambrian shell fossils and *Burgess-type exceptionally well-
preserved fossil deposits ("lagerstatten"). This hypothesis
suggests that animal phyla originated rather suddenly
approximately 580 million years ago during the *Proterozoic-
Phanerozoic transition. The alternative hypothesis (called "slow
burn") suggests that animals developed more slowly, first
appearing, according to some molecular analyses, more than 1
billion years ago. ... ... A. Seilacher et al now report data
from the Mesoproterozoic Chorhat Sandstone site in central India.
The authors report that certain *bedding plane features are
biological and can be interpreted as the burrows of wormlike
undermat miners (i.e., *infaunal animals that excavated tunnels
underneath *microbial mats). The authors suggest these burrows
indicate that *triploblastic animals existed more than a billion
years ago. The authors further suggest their evidence indicates
that the diversification of animal designs proceeded very slowly
before the appearance of organisms with hard skeletons during the
Cambrian evolutionary explosion, and that the diversification
occurred before the ecological changes that accompanied that
explosion.
-----------
A. Seilacher et al (3 installations, DE IN US)
Triploblastic animals more than 1 billion years ago: Trace fossil
evidence from India.
(Science 2 Oct 98 282:80)
QY: Friedrich Pfluger, Yale University, 203-432-4771.
-----------
Text Notes:
... ... *metazoans: In general, the term "metazoa" refers to all
multicellular animals. Among important distinguishing
characteristics of metazoa are cell differentiation and
intercellular communication. For certain multicellular colonial
entities such as sponges, some biologists prefer the term
"parazoa".
... ... *Cambrian: Refers to the approximate general time-frame
500 to 600 million years ago (but often considered as 505 to 545
million years ago).
... ... *Burgess-type: The Burgess Shale fossil deposit site in
British Columbia (CA) is apparently a geological accident of
superb preservation, and one that has revealed to paleontologists
the limitations of their views of the varieties of life in the
*Cambrian period. All the fossils expected for the Cambrian are
found in the Burgess Shale, but studies have demonstrated in
addition a remarkable array of perfectly preserved soft-bodied
animals, including a variety of worms, *arthropods, sponges,
*brachiopods, and some bizarre forms seemingly unrelated to any
known groups. The consequence was a new appreciation among
paleontologists of the tremendous increase in metazoan diversity
that apparently occurred during the Cambrian period, and indeed
this increase is now considered one of the most important events
in the history of life on Earth. 
... ... *arthropods: The largest phylum in the Animal Kingdom in
terms of both number of taxa and biomass, but the taxonomy has
undergone revision, and it is now essentially an informal
classification. In general, the arthropods are characterized by a
tough chitinous protective covering (exoskeleton) flexible only
at the joints (e.g., insects).
... ... *brachiopods: A phylum of bivalve coelomate invertebrates
resembling bivalve molluscs. The term "bivalve" refers to the
presence of a hinged shell; the term "coelomate" refers to the
presence of a true body cavity.
... ... *Proterozoic-Phanerozoic transition: The Proterozoic eon
is the time-frame 2600 million years ago to 600 million years
ago. The Phanerozoic eon is the time-frame 600 million years ago
to the present. During the Phanerozoic, atmospheric oxygen
apparently increased by a factor of 10 to its present value.
... ... *bedding plane: A distinct surface separating two
strata, the bedding plane marking a break in the continuity of
sedimentation, a break that can be caused by a period of erosion
or a cessation of sediment supply.
... ... *infaunal: Refers to an organism that burrows into the
substrate.
... ... *microbial mats: A dense microbial layer. The authors
propose this served as a food source for wormlike animals
exploiting its decaying base.
... ... *triploblastic animals: These are animals with a body
organization derived from 3 germ layers (ectoderm, endoderm,
mesoderm). The category includes all metazoans except
*coelenterates, which are diploblastic.
... ... *coelenterates: A phylum of mostly marine multicellular
animals. (e.g., jellyfish).
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 30Oct98


3. ON THE ORIGIN OF RNA
Central to any theory of the origin of life on Earth is a theory
of the formation of nucleic acid structures under prebiotic
conditions. Systematic chemical studies indicate that the
capability of *Watson-Crick nucleotide base-pairing is widespread
among non-biological nucleic acid alternatives, and a comparison
of RNA and such alternatives with regard to chemical properties
fundamental to the biological function of RNA can provide clues
to the origin of RNA. ... ... Albert Eschenmoser (Scripps
Research Institute, US) reviews this field, the author making the
following points concerning research strategies:
     1) The term "chemical etiology", as applied to nucleic acid
structures, refers to systematic experimental studies aimed at
determining why *ribofuranosyl nucleic acids, rather than some
other family of molecular structures, came to be the molecular
basis of life's genetic system. The quest is to uncover the
criteria for nature's choice. Understanding these criteria in
chemical terms would constitute a central element of any theory
of the origin of the particular kind of chemical life known
today.
     2) The general strategy of research in this area is to
conceive (via chemical reasoning) potential natural alternatives
to the nucleic acid structure, to synthesize such alternatives by
chemical methods, and to compare the alternative structures with
the natural nucleic acids with respect to those chemical
properties that are fundamental to the biological function of RNA
and DNA.
     3) Basic to this research is the supposition that the RNA
structure originated through a combinatorial process, within the
domain of sugar-based oligonucleotides, with respect to the
assembly and functional selection of an informational system. The
research can be viewed as an attempt to mimic the selectional
part of such a hypothetical natural process by chemical means.
     4) Remaining open to question is not only the potential of
RNA (or of any RNA alternative) for nonenzymatic replication, but
also its chances for formation in an abiotic natural environment.
Although there is a consensus that the building blocks of RNA
(sugars, purines, and pyrimidines) are of potential prebiotic
origin, and although the broad chemical contours of an assembly
of the RNA structure from such building blocks seem clear,
convincing experimental evidence that such a process can in fact
occur under possible natural conditions is still lacking. Much
more experimental work on the problem is needed before a
chemically reliable assessment of an abiotic origin of RNA (or of
any RNA alternative) can be made.
     5) In principle, a chemical etiology of nucleic acid
structure has to reckon with the possibility that the RNA
structure might have originated as a consequence of synthetic
contingency, and not as a result of synthetic variation coupled
with functional selection. Thus, circumstances may have favored
the selective formation of the RNA structure in preference to
alternatives in an abiotic or a biotic environment. This would
imply a synthetic rather than a functional selection as the
primary determinant in the emergence of RNA. If this was the
case, then the chemical study of nucleic acid alternatives, and
the discovery of efficient informational nucleotide base-pairing
systems, would acquire an altered importance, namely, that it
would provide chemical facts concerning the uniqueness of RNA and
of the kind of life now known.
     6) The author concludes: "The aim of an experimental
etiological chemistry must be not primarily to show how life on
Earth could have originated, but to provide decisive experimental
evidence -- through the realization of model systems in the
laboratory ('artificial chemical life') -- that life can arise as
a result of the organization of organic matter."
-----------
Albert Eschenmoser: Chemical etiology of nucleic acid structure.
(Science 25 Jun 99 284:2118)
QY: Albert Eschenmoser, Scripps Research Institute 619-784-1000.
-----------
Text Notes:
... ... *Watson-Crick nucleotide base-pairing: In the Watson-
Crick helix, the helical structure assumed by two strands of DNA
is held together throughout the length of the strands by hydrogen
bonds between bases on opposite strands. Each member of a base-
pair belongs to a different polynucleotide chain. Adenine is
always paired with thymine and guanine is always paired with
cytosine. Such an array of nucleotide base-pairs is referred to
as "Watson-Crick base-pairing".
... ... *ribofuranosyl nucleic acids: (ribosyl nucleic acids) In
general, a "ribosyl" is any glycosyl group formally derivable
from the alpha- or the beta-furanose forms of D- or L-ribose. RNA
is a (3' -> 5')-pentofuranosyl.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 10Sep99
-------------------
Related Background:
RNA-CATALYZED NUCLEOTIDE SYNTHESIS
In research concerning the origin of life on Earth, the "RNA
world" hypothesis proposes that early life developed by making
use of RNA molecules, rather than proteins, to catalyze the
synthesis of important biological molecules. It is believed,
however, that the nucleotides constituting RNA were scarce on
early Earth, so that RNA-based life must have acquired the
ability to synthesize RNA nucleotides from simpler and more
readily available precursors such as sugars and bases. Apparently
plausible prebiotic synthesis routes have been proposed for
sugars, sugar phosphates, and the 4 RNA bases, but the coupling
of these molecules into nucleotides, specifically pyrimidine
nucleotides, poses a challenge to the RNA world hypothesis.
... ... P.J. Unrau and D.P. Bartel report the application of in
vitro selection to isolate RNA molecules that catalyze the
synthesis of a pyrimidine nucleotide at their *3' terminus. The
authors suggest the finding that RNA can catalyze this type of
reaction, which is modeled after pyrimidine synthesis in
contemporary metabolism, supports the idea of an RNA world that
included nucleotide synthesis and other metabolic pathways
mediated by *ribozymes.
-----------
P.J. Unrau and D.P. Bartel (Massachusetts Institute of
Technology, US): RNA-catalyzed nucleotide synthesis.
(Nature 17 Sep 98 395:260)
QY: David P. Bartel, Mass. Inst. of Technology 617-253-1000.
-----------
Text Notes:
... ... *3' terminus: Both DNA and RNA are polymers whose
constituent nucleotides are linked by 3',5'-phosphodiester bonds,
and the polymers have polarity, with one end a 5'-end unattached
and the other end a 3'-end unattached. This asymmetry is mirrored
in the differing functional involvement of the 2 ends in various
biochemical events in the living cell.
... ... *ribozymes: First discovered in 1981, ribozymes (not to
be confused with riboSOMES) are a small group of RNA molecules 
that act as enzymes. They are found in the ciliate protozoan
Tetrahymena, and they are intriguing because they defy the usual
rule that enzymes are proteins.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 9Oct98
-------------------
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 August) (Science-Week 5 Sep 97)


4. BACTERIA: CHAPERONES AND PROTEIN ASSEMBLIES
A bacterium is a single-cell organism without a nucleus (a
"prokaryote"). There is no differentiation of cells and tissues
into various specialized structures because there are no tissues
and only one cell, that of the organism itself. All specialized
structures in a bacterium are molecular structures, and some of
these (e.g., rotating bacterial flagella) are of exquisite design
and striking examples of complex architecture and dynamics at the
molecular level [*Note #1]. The surface of a bacterium is
complicated, more complex than the surfaces of many types of
"higher-level" eukaryotic cells (cells with internal membrane-
bound organelles such as a nucleus). Nearly all bacteria can be
divided into two groups depending on their ability or inability
to retain a crystal violet-iodine complex when exposed to an
organic solvent such as acetone or alcohol. Those bacteria that
retain the complex are called "gram-positive"; those bacteria
that cannot retain the complex are called "gram-negative" -- in
both cases, after Hans Christian Gram (1853-1938), who was the
first to describe the staining procedure in 1884. Although the
Gram reaction is not completely understood, it is intimately
related to the structure of the bacterial cell wall, a rigid
structure that encloses the bacterial organism, and which has
known differences in chemical composition between the two types
of Gram-reactive bacteria. Concerning gram-negative bacteria,
many such bacteria possess rigid surface appendages called "pili"
(Latin for "hairs") or "fimbriae" (Latin for "fringes"). These
structures are 7 nanometers in diameter, and much shorter and
thinner than flagellae (which are 25 nanometers in diameter).
Pili are composed of structural protein subunits called "pilins".
Some pili contain a single type of pilin, while others contain
more than one type. Minor proteins, located at the tips of the
pili, are responsible for attachment properties of the pili and
play a role in the adherence of bacteria to host cells. In fact,
the virulence of certain pathogenic bacteria is now recognized to
depend not only on toxins secreted by the bacteria, but also on
the adherent properties of their pili. The pilin molecules that
compose the pili structure are arranged helically to form a
straight cylinder that does not rotate (as a flagellum does) and
which, unlike a flagellum, lacks a complete special base
structure (basal body) in the bacterial cell membrane. Like other
complex structures in cells, pili consist of precise
architectural arrangements of one or more types of proteins, and
an important question is how are these arrangements of
macromolecules achieved? It is now apparent that "molecular
chaperones" -- proteins found in all cells that help other
proteins to fold and assemble -- are involved in the construction
of bacterial pili. ... ... David Eisenberg (University of
California Los Angeles, US) presents a commentary on current
research in this field, with a focus on recent work by *Choudhury
et al (1999) and *Sauer et al (1999). Eisenberg makes the
following points:
     1) The apparent duty of one family of molecular chaperones
is to coordinate the assembly of pilin protein subunits into
adhesive pili. The chaperones bring the subunits one by one to a
large channel protein (the "usher") in the bacterial outer
membrane, and there the pilins are released and become attached
to each other to form the pilus, which is composed of a thick rod
connected to a thin tip (the "fibrillum") by adaptor proteins.
     2) Since the pioneering experiments of *Anfinsen in the
middle of this century, biochemists have believed that it is
simply the order of the amino acids in a protein that determine
how it folds into a 3-dimensional structure and assembles into
complexes with other proteins. Yet Anfinsen himself realized that
this simple "thermodynamic hypothesis" is open to many
refinements, with Anfinsen stating: "Another large molecule (for
example, an antibody, another protein, or possibly even the same
protein) could influence the folding process by intermolecular
interactions."
     3) We now know that there are more than 20 families of
molecular chaperones that assist in the noncovalent assembly of
protein structures. Furthermore, there are many cases where
interaction of a protein molecule with another of its kind
influences the structure of both.
     4) It has always been assumed that the main function of
molecular chaperones is to somehow protect folding proteins from
associating prematurely and forming insoluble aggregates. But how
do they do this? Although there are many current ideas about how
a molecular chaperone might protect newly synthesized protein
chains from associating with each other as they fold, no
definitive mechanism has yet been identified.
     5) Both Choudhury et al (1999) and Sauer et al (1999)
present the crystal structure of a complex between a bacterial
molecular chaperone and its associated pilin subunit. Both
structures offer graphic pictures of a molecular chaperone at
work: The chaperone configurationally complements the molecule
that it is protecting, forming a stable water-soluble complex,
and prevents the chaperoned protein from prematurely coupling
with other molecules. The chaperone carries the pilin subunit to
the large pore protein (the usher), where the pilin subunit is
released by the chaperone and becomes attached to the inward end
of the growing pilus rod.
-----------
David Eisenberg: How chaperones protect virgin proteins.
(Science 13 Aug 99 285:1021)
QY: David Eisenberg [david@mbl.ucla.edu]
-----------
Text Notes:
... ... *Note #1: Bacteria are indeed "primitive" organisms. But
consider the vital statistics: Each bacterium contain 4000 or
5000 distinctly different proteins, each protein type a separate
functional entity, and most of these proteins are precisely and
dynamically arranged in space in a system that completely
replicates itself approximately every 20 minutes. There are no
trivialities when confronting such an apparatus.
... ... *Choudhury et al (1999): Science 7 Aug 99 285:1061
... ... *Sauer et al (1999): Science 7 Aug 99 285:1058
... ... *Anfinsen: The entire folding architecture of a complex
protein must be precisely constructed in order for protein
functionality to exist. Which provokes the question of how the
specific folding of particular proteins is ensured by the
biological system. The answer is evident for simple proteins in
vitro: the final configuration is predetermined by the amino acid
sequence, there being a single energetically favored
configuration that will always be attained at equilibrium. This
is "Anfinsen's Rule", first proposed by the protein biochemist C.
B. Anfinsen (1916-1995) more than 30 years ago. In vivo, however,
and particularly for complicated proteins, the situation is more
involved, as Anfinsen himself recognized. Anfinsen received the
Nobel Prize for Chemistry in 1972.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 10Sep99


5. TUMOR VIRUSES AND ONCOGENES
     Viruses, first discovered in 1892 [*Note #1], are infectious
agents that are smaller than biological cells such as bacteria,
their size ranging from about 20 nanometers to about 900
nanometers. Beginning in the 1930s, there was much controversy
about classification, with the central question whether viruses
are a "life" form. The answer, of course, depends on the
definition of "life", and since there are various definitions
possible, the question is ill-defined. In general, a virus is a
self-organizing molecular system capable of using living cells to
replicate itself, the sequence of events in many cases altering
or destroying the cells and thus causing a disease process.
     In addition to disease processes caused by the destruction
of cells, viruses are now known to be etiologic factors in the
development of several types of human tumors, including two of
worldwide significance: cervical cancer and liver cancer. Viruses
have also been strongly associated epidemiologically with other
human cancers, and these viruses include *human papillomavirus,
*Epstein-Barr virus, and *hepatitis B virus.
     Like other viruses, tumor viruses are classified among
different virus families according to the nucleic acid of their
genome and the biophysical characteristics of their virions
(virion = the complete virus particle as it exists outside the
host cell). All known tumor viruses either have a DNA genome or
an RNA genome. In the case of an RNA genome, the RNA genome
generates a DNA "provirus" (a preliminary virus entity) after
infection of cells. All RNA tumor viruses (i.e., tumor viruses
with an RNA genome) belong to the "retrovirus" family.
Retroviruses carry an RNA-directed polymerizing enzyme (reverse
transcriptase) that constructs a DNA copy of the RNA genome of
the virus. This DNA copy (the provirus) becomes integrated into
the DNA of the infected host cell, and it is from this integrated
DNA that all proteins of the virus are translated.
     Tumor viruses are of two general types with respect to tumor
induction, distinguished by (among other things) whether or not
they carry "oncogenes" (i.e., any gene associated with the
causation of cancer). All DNA tumor viruses carry oncogenes,
these oncogenes an integral part of the viral genome and not
derived from host cells. Of RNA tumor viruses, there are two
types: a) the highly oncogenic ("direct-transforming") RNA tumor
viruses (class I RNA tumor viruses) carry an oncogene of host-
cell origin; b) the weakly oncogenic ("slowly transforming") RNA
tumor viruses (class II RNA tumor viruses) do not contain an
oncogene but induce leukemias after long incubation periods by
indirect mechanisms. In this context, the term "transforming"
refers to the transformation of a normal host-cell into a cancer
cell. ... ... George Klein (Karolinska Institute, SE) presents an
essay on the history of the idea of tumor viruses, the author
making the following points:
     1) In 1911, Peyton Rous (1879-1970) demonstrated that fowl
*sarcomas could be transmitted with cell-free filtrates, and the
rapid consensus was that cancer was a viral disease. But when
similar experiments with mouse and rat tumors failed soon after,
it was concluded that tumor viruses occurred only in birds, and
the field fell into disrepute.
     2) The discovery in the 1920s of the Shope papilloma virus,
which causes warts in rabbits, produced little enthusiasm among
researchers because the tumors were largely benign.
     3) In the 1930s, the mouse mammary tumor virus was
discovered, and this virus was called "*milk factor" rather than
"milk virus" to avoid a negative reaction from people in the
medical science community who had relegated tumor viruses to the
cabinet of freaks.
     4) The great change in the climate of opinion concerning
tumor viruses came in the 1950s when Ludvik Gross discovered the
mouse leukemia virus, and Sarah Stewart and Bernice Eddy
identified the *polyomavirus. Within a few years the pendulum had
swung to the opposite extreme. After decades of failed attempts,
viruses that could induce tumors in mammals were now isolated in
quick succession. Tumor virology rapidly became favored by grant-
giving agencies, and the oncogene concept -- that tumor viruses
carry "cancer genes" that can transform some of their target
cells into a cancerous or precancerous state -- was formulated in
the context of this enthusiasm.
     5) The class I RNA tumor viruses can induce tumors because
they have accidentally incorporated from host cells genes that
regulate growth. After entering a new host cell, the viral enzyme
reverse transcriptase copies the viral RNA into provirus DNA
which integrates randomly into the host cell DNA. When the virus
starts to reproduce itself, and the proviral DNA is transcribed
back into RNA, some of the new virus particles may also carry
additional cellular sequences from regions adjacent to the random
integration site of the proviral DNA. These newly replicated
virus particles have the potential to corrupt the DNA of other
host cells when these host cells are subsequently infected.
     6) Class II RNA tumor viruses do not themselves contain
oncogenes, but contribute to malignant tumor development
relatively infrequently when their proviral DNA happens to
integrate into the host DNA near host oncogenes.
     7) By discovering cellular genes that regulate growth and
that can contribute to cancer development after illegitimate
viral activation, the virologists demonstrated the existence of
host oncogenes that when mutated can promote cancer formation
independent of viruses. This discovery once again relegated tumor
virology to a less prominent place and reaffirmed the sovereignty
of cell biology. Cancer is essentially a disease of cellular DNA;
when viruses are involved in cancer, they are involved as one of
many possible DNA-corrupting agents.
     8) All oncogenes have turned out to be *highly conserved
housekeeping genes that participate in the regulation of the
*cell cycle. Their potentially tumorigenic forms drive the cell
towards proliferation. For overt tumor development, additional
genetic changes are required, including loss of *cell-cycle
check-point controls, inhibition of programmed cell death
(apoptosis), and *up-regulation of blood supply (*angiogenesis).
The current oncogene field, therefore, emerged from erroneous
concepts concerning the etiology of cancer, but these concepts,
when combined with several decades of diligent experimentation,
finally produced a valuable outline of the events that cause the
formation of cancerous tumors.
-----------
George Klein: The tale of the great cuckoo egg.
(Nature 5 Aug 99 400:515)
QY: George Klein, Karolinska Institute, PO Box 280, S-171, 77
Stockholm, SE.
-----------
Text Notes:
... ... *Note #1: In 1892, a Russian botanist named Dmitri
Ivanovsky (1864-1920) became interested in the cause of a disease
of the valuable tobacco plant, a disease called "mosaic disease".
The name was due to the mosaic patterns the disease produced on
the leaves of the plant. Ivanovsky devised an experiment, mashed
up infected leaves, and forced them through filters designed to
remove all bacteria. He discovered that the liquid that passed
through the filters could still infect healthy tobacco plants.
Ivanovsky concluded, in error, that the infectious agent was
still a bacterium, but that his filters were somehow defective,
and it was this conclusion that he published in a Russian
scientific journal. Six years later, a Dutch botanist named
Martinus Beijerinck (1851-1931) repeated the experiments and
concluded the infectious agent was not a bacterium but the liquid
itself, a poison, and he called it a filterable "virus", the word
"virus" being the Latin word for poison. In the 1930s, an
American biochemist named Wendell Meredith Stanley (1904-1971)
became interested in this mysterious "virus" liquid. He believed
the poison to be a protein. He repeated the filtration
experiments with diseased tobacco leaves, and he isolated a
crystalline substance in high concentration that had all the
infective properties of the so-called virus liquid. In the report
which Stanley published in 1935, he concluded: "Tobacco mosaic
virus is regarded as an autocatalytic protein which, for the
present, may be assumed to require the presence of living cells
for multiplication." For this work, Stanley received the Nobel
Prize in Chemistry in 1946. Although the tobacco mosaic virus,
like all viruses, is much more than just a simple autocatalytic
protein, the first understanding of the true nature of viruses
was now in place. The experiments that had begun in Russia in
1892 culminated 43 years later in the startling realization that
an entire class of infectious agents much smaller than bacteria
existed.
... ... *human papillomavirus: The papillomavirus causes benign
tumors called "warts". The virus in its extracellular form
(virion) is 55 nanometers in diameter, with a circular double-
stranded DNA genome of approximately 8000 nucleotide base pairs.
The virus primarily infects surface *epithelia. There are more
than 70 different types of human papillomaviruses.
... ... *epithelia: In animals, epithelial cells compose the cell
layers that form the interface between a tissue and the external
environment, for example, the cells of the skin, the lining of
the intestinal tract, and the lung airway passages.
... ... *Epstein-Barr virus: The Epstein-Barr virus is a large
ubiquitous herpesvirus that is the causative agent of acute
infectious mononucleosis and a factor in the development of
nasopharyngeal carcinoma, Burkitt's lymphoma, and other
disorders. The virion is approximately 100 nanometers in
diameters, and contains a double-stranded DNA genome consisting
of approximately 172,000 nucleotide base pairs.
... ... *carcinoma: In general, a carcinoma is any malignancy
derived from epithelial tissue.
... ... *hepatitis B virus: The hepatitis B virus is the
causative agent of *serum hepatitis. The virion is 42 nanometers
in diameter, the genome double-stranded DNA with 3200 nucleotide
base pairs.
... ... *serum hepatitis: In general, "hepatitis" is any
inflammation of the liver. "Serum hepatitis" is usually
transmitted by injection of infected blood or blood derivatives,
or by the use of contaminated needles or other instruments.
... ... *sarcomas: A sarcoma is a connective tissue neoplasm,
usually highly malignant.
... ... *milk factor: The prototype of RNA tumor viruses is the
"mouse mammary tumor virus", which occurs in high-mammary-cancer
strains of inbred mice, and is found in particularly large
amounts in lactating mammary tissues and milk. The virus is
readily transferred to suckling mice, in whom the incidence of
subsequent development of carcinoma of the breast is high. The
work of J.J. Bittner (1904-1961) on this virus is classic: In the
1930s, carefully inbred strains of mice were kept for research on
cancer. Some strains were highly resistant to cancer and rarely
developed it, while other strains were so prone to cancer that
almost every individual animal developed the disease. In 1936,
Bittner established that if young mice of a cancer-resistant
strain were transferred to the breast of a foster mother of a
cancer-prone strain, the young mice developed cancer in the
course of their lives. If, on the other hand, young mice of a
cancer-prone strain were fed at the breast of a foster mother of
a cancer-resistant strain, they did not usually develop cancer.
The Bittner "milk factor" was isolated in 1949 and was found to
consist of virus-like particles containing nucleic acid.
... ... *polyomavirus: Papillomaviruses and polyomaviruses are
the two classes of papovaviruses. Like papillomaviruses,
polyomaviruses have a double-stranded DNA genome, but with only
5000 nucleotide base pairs. The polyoma virion is 45 nanometers
in diameter, and the target tissues are internal organs. An
important research tool, the SV40 monkey virus, is a
polyomavirus.
... ... *highly conserved housekeeping genes: The term "highly
conserved" refers to a gene sequence maintained across
evolutionary time. So-called "housekeeping" genes are genes
coding for proteins involved in essential functions such as
metabolic cycles.
... ... *cell cycle: The "cell cycle" is the name given to the
ordered sequence of phases through which a cell passes from one
mitotic cell division to the next.
... ... *cell-cycle check-point controls: So-called "checkpoints"
are points in the cell division cycle where the cycle can be
halted until conditions are suitable for the cell to proceed to
the next stage.
... ... *up-regulation: In general, the term "up-regulation"
refers to an increase in the activity of some entity or process.
... ... *angiogenesis: 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 (up-regulation of a blood supply) 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.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 10Sep99


6. ON ESTROGEN AND THE CARDIOVASCULAR SYSTEM
Hormones are signaling molecules secreted into the blood stream
by endocrine cells (i.e., cells that secrete internally) and
acting on target cells that possess receptors for the hormone.
Estrogen is a collective term for the female hormones, the most
powerful of which is *estradiol. They control female secondary
sexual characteristics, and prepare and maintain the uterine
lining. Estrogen affects the growth, differentiation, and
function of peripheral tissues of the reproductive system,
including the mammary gland, uterus, vagina, and ovary. Estrogens
also play an important role in bone maintenance and exert
cardioprotective effects. In the brain, estrogens modulate
physiological parameters important for regulating procreation,
including reproductive behavior, *gonadotropin production and
release from the pituitary, and mood. In general, there are two
estrogen *receptors, estrogen receptor alpha and estrogen
receptor beta, both of which are members of the superfamily of
steroid hormone receptors. Estrogen receptors alpha and beta have
considerable amino acid sequence similarities and, like all
steroid hormone receptors, are *transcription factors that alter
*gene expression when they are activated. Estrogen receptors are
activated by estrogen binding, but they can also be activated by
*growth factors in the absence of estrogen.
... ... M.E. Mendelsohn and R.H. Karas (Tufts University, US)
present a review of current research on the protective effects of
estrogen on the cardiovascular system, the authors making the
following points:
     1) The incidence of cardiovascular disease differs
significantly between men and women, in part because of
differences in risk factors and hormones. The incidence of
*atherosclerotic disease is low in premenopausal women, rises in
postmenopausal women, and is reduced to premenopausal levels in
postmenopausal women who receive estrogen therapy.
     2) Until recently the atheroprotective effects of estrogen
were attributed principally to the effect of the hormone on serum
lipid concentrations. However, estrogen-induced changes in serum
lipids account for only approximately one-third of the observed
clinical benefits of estrogen. Current data suggest that the
direct actions of estrogen on blood vessels contribute
substantially to the cardiovascular protective effects of
estrogen. The vasculature, like bone, liver, brain, and
reproductive tissues, is now recognized as an important target of
the action of estrogen.
     3) Estrogen increases vasodilation, inhibits the response of
blood vessels to injury, and inhibits the development of
atherosclerosis. Estrogen-induced vasodilation occurs 5 to 20
minutes after estrogen has been administered and is not dependent
on changes in gene expression ("nongenomic action"). The
estrogen-induced inhibition of the response to vascular injury
and the protective effect of estrogen against atherosclerosis
occur over a period of hours or days after estrogen treatment and
are dependent on changes in gene expression in the vascular
tissues ("genomic actions").
     4) Blood vessels are complex structures, with walls
containing *smooth-muscle cells and an *endothelial lining, both
of which bind estrogen with high affinity. Estrogen receptor
alpha has been found in both types of vascular cells in women and
men, as well as in muscle cells of the heart (myocardial cells).
Estrogen receptor beta is found in many tissues, and is also
present in nonhuman primate and human arteries and veins, as well
as in the blood vessels of normal mice and rats, and in the blood
vessels of mice in which the gene for estrogen receptor alpha has
been disrupted.
     5) The mechanisms that mediate the rapid effects of estrogen
on the blood vessel wall are not fully understood. Current data
suggest that estrogen influences the bioavailability of
endothelial-derived *nitric oxide and, through nitric-oxide
mediated increases in *cyclic guanosine monophosphate (cGMP),
causes the relaxation of vascular smooth-muscle cells. The longer
term effects of estrogen, about which more is known, are due at
least in part to changes in vascular-cell gene expression that
are mediated by estrogen receptors alpha, beta, or both.
Estrogen-regulated proteins influence vascular function in an
*autocrine or *paracrine fashion, and additional vascular target
genes regulated by estrogen receptors need to be identified.
     6) The authors conclude: "It is likely that the rapid
progress in this field in both basic and clinical sciences will
soon lead to the development of more specific hormonal therapies
for cardiovascular disease."
-----------
M.E. Mendelsohn and R.H. Karas: The protective effects of
estrogen on the cardiovascular system.
(New England J. Med. 10 Jun 99 340:1801)
QY: Michael E. Mendelsohn [michael.mendelsohn@nemc.org]
-----------
Text Notes:
... ... *estradiol: 1,3,5(10)-estratriene-3,17beta-diol.
C(sub18)H(sub24)O(sub2). This is the natural hormone.
... ... *gonadotropin: (gonadotrophin, gonadotrophic hormone)
Refers to a group of hormones capable of promoting growth and
function of the gonads.
... ... *receptors: In the context of biochemistry and molecular
biology, a "receptor" is a protein or part of a protein on the
cell surface that processes molecular signals, conveying the
signals to the interior of the cell with or without a mediation
of function. The term "receptor" is also used in physiology and
neurobiology, where it refers to cells specialized to respond to
specific physical and chemical stimuli: e.g., the receptor cells
of the retina, the rods and cones, which respond to incident
light.
... ... *transcription factors: Transcription is the process by
which the genetic information in DNA is converted into RNA, and
"transcription factors" are a class of DNA-binding proteins that
regulate RNA transcription.
... ... *gene expression: In general, the term "gene expression"
includes any gene activity, but particularly an activity that
produces the synthesis or activation of a specific protein. 
... ... *growth factors: Growth factors are peptide hormones that
regulate the growth of cells and tissues.
... ... *atherosclerotic disease: The term "arteriosclerosis"
refers to any hardening of the arteries, and "atherosclerosis" is
a type of arteriosclerosis characterized by irregularly
distributed lipid deposits on the internal walls of large and
medium-sized arteries. Such deposits can be provoked by various
types of damage of the internal arterial walls, including damage
caused by high blood pressure, tobacco smoking, toxic substances,
etc.
... ... *smooth-muscle cells: Smooth muscle was originally
differentiated from striated muscle on the basis of microscopic
appearance, but there are important other differences both
functional and molecular, and in general smooth muscle is
specialized for slow sustained contractions such as those
involved in the control of the diameters of blood vessels.
... ... *endothelial lining: The "endothelium" is a layer of flat
cells lining blood vessels, lymphatic vessels, the heart, etc.
... ... *nitric oxide: The gas nitric oxide is the prime member
of an entirely new class of neurotransmitters discovered only in
the 1990s. Among other involvements, it is released from
endothelium in response to acetylcholine and other vasodilators,
with a resultant relaxation of blood vessels. Nitric oxide is a
free radical with a half-life of only a few seconds, and its
concentration in tissues is difficult to establish
quantitatively. It should not be confused with nitrous oxide
("laughing gas"), which is an analgesic gas used as an auxiliary
in anesthesia in dentistry and surgery.
... ... *cyclic guanosine monophosphate (cGMP): (guanosine 3',5'-
phosphate) A monophosphoric diester of guanosine found in almost
all mammalian tissues; a cyclic nucleotide similar in structure
and the regulation of its metabolism to cyclic AMP (adenosine
3',5'-phosphate). Like cyclic AMP, cyclic GMP acts as a "*second
messenger" in  many systems.
... ... *second messenger: The "first messenger" is the hormone
that interacts with its receptor (target cell) on the cell
surface. The "second messenger" is intracellular, and transmits a
signal from a cell-surface receptor (or components associated
with a cell-surface receptor) to target entities inside the cell.
... ... *autocrine: In general, an "autocrine" effect is the
action of a local hormone on the same cell which secreted the
hormone.
... ... *paracrine: Paracrine mechanisms are localized chemical
regulatory mechanisms  -- i.e, mechanisms involving local
hormones, as opposed to hormones that act systemically.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 10Sep99


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

IN FOCUS: ON PHYSICAL OPTICS AND EARLY 20TH CENTURY PHYSICS
"In relativity theory the velocity of light enters as a
fundamental constant, but the development of quantum theory bears
a much more important and also a symbiotic relation to optical
theorizing. Concepts drawn from optics and also optical phenomena
(such as *line spectra and the *photo-electric effect) were
historically important in framing quantum theory, while that
theory, in turn, provided new insights into the nature of light.
In 1902 Philipp Lenard [1862-1947] made the problematic discovery
that, contrary to the wave theory, there was not a direct
relation between the intensity of light falling on a photo-
electric cell and the energy of displaced electrons, but that the
energy depended solely on the wavelength. This anomaly was
explained by Albert Einstein (1879-1955) in 1905 on the
assumption, derived from Max Planck, that radiation is quantized,
a quantum possessing the energy hf, h being Planck's constant,
and f the frequency. Einstein also later attributed to the light
quantum a momentum hf/c [where c is the velocity of light], and
he conceived a light quantum as a singular point surrounded by a
vector field which decays with distance. Crucial insight into the
nature of radiation was provided in 1923 by Arthur Holly Compton
[1892-1962] who discovered that in the scattering of x-rays from
free electrons, the wavelength of the scattered radiation was
greater than the incident radiation. This phenomenon indicated
that the radiation, including light, is quantized. While this
conclusion impressively supported Einstein's conception of the
photon, Niels Bohr [1885-1962] pressed in 1927 for a dualistic
account according to which light sometimes behaves like a wave,
sometimes like a particle. If most physicists in the 1830s
believed that the nature of light could be known, their
descendants of the 1930s could only offer an account of how light
behaves under specified experimental conditions. For Bohr and his
followers the question 'what is light' can no longer be asked."
-----------
G.N. Cantor: Physical Optics.
In R.C. Olby et al: Companion to the History of Modern Science.
(Routledge, London 1990, p.636)
-----------
[Editor's note: Of relevance is the following quotation:
"All these fifty years of conscious brooding have brought me no
nearer to the answer to the question, `what are light quanta?'
Nowadays every Tom, Dick, and Harry thinks he knows it, but he is
mistaken." -- Albert Einstein]
-----------
Text Notes:
... ... *line spectra: Emission and absorption spectra may show a
continuous spectrum, a line spectrum, or a band spectrum. A
continuous spectrum contains an unbroken sequence of frequencies
over a relatively wide range, and is produced by incandescent
solids, liquids, and compressed gases. Line spectra are
discontinuous lines produced by excited atoms and ions as they
fall back to a lower energy level. Band spectra (i.e., closely
grouped bands of lines) are characteristic of molecular gases or
chemical compounds.
... ... *photo-electric effect: This effect concerns the
liberation of electrons from a substance exposed to
electromagnetic radiation. The number of electrons emitted
depends on the intensity of the radiation, while the kinetic
energy of the electrons emitted depends on the frequency of the
radiation. The effect appears as a quantum process in which the 
radiation is considered as a stream of photons, each having an
energy hf, where h is Planck's constant and f is the frequency of
the radiation.
-------------------
Notes by SCIENCE-WEEK [http://scienceweek.com] 10Sep99


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