ScienceWeek

SCIENCE-WEEK

A Weekly Digest of the News of Science

September 18, 1998

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We may or may not be majestic as a species,
but if one considers an astronomer sitting alone
on a cold night at a telescope on a mountain top,
one must conclude we are certainly obsessed with
knowing what and where we are.
-- Anonymous

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Contents of This Issue:

1. Monkeypox, Smallpox, and Biological Terrorism
2. White Dwarf Stars and Gravitational Microlensing
3. Experimental Evidence for Microscopic Chaos
4. Response of Single DNA Molecules to Sudden Elongational Flow
5. Evolution: Dinoflagellate Ancestors in the Early Cambrian
6. Evolution: Clay Mineral Variation in Burgess Shale Fossils
7. A New Method for Following Individual Cells in Slime Mold
8. New Evidence Concerning Evolution of the Immune System
9. Analysis of Lateral Domains in Cell Membranes
10. On the Bacterium Staphylococcus Aureus

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1. MONKEYPOX, SMALLPOX, AND BIOLOGICAL TERRORISM
The last case of confirmed smallpox on Earth occurred more than
20 years ago, and nearly 2 decades ago the World Health
Organization concluded the global eradication of smallpox had
been achieved. But new questions have now arisen: a) Could recent
outbreaks of human monkeypox in Africa represent the return of
another form of smallpox? b) Could smallpox virus be used as a
weapon of biological terrorism? c) What are the implications of
the decision of the World Health Organization to advise the
destruction of all isolates of the smallpox virus in June 1999?
... ... In a short review of these questions, Breman and
Henderson make following points: 1) The available data do not
support the possibility that monkeypox might soon take over the
ecological niche left vacant by smallpox. 2) All vaccination
against smallpox ceased after eradication of the disease was
affirmed. Virtually all children and many adults are now fully
susceptible to smallpox. Only limited supplies of vaccine are
available. 3) Were smallpox virus released by an act of
terrorism, the results could be catastrophic. A large proportion
of the population has no immunity. There is little available
vaccine and no effective treatment. The expected case fatality
rate would be higher than 25 percent. The authors conclude:
"Reports suggesting that monkeypox might replace smallpox as a
serious epidemic threat are unsubstantiated, but the threat posed
by the possible use of smallpox as a terrorist weapon is genuine.
Because of the gravity of this threat, all known stocks of
variola [smallpox] virus should be destroyed as soon as possible.
The deliberate deployment of this virus must be discouraged by
whatever means possible."
-----------
J.G. Breman and D.A. Henderson (2 installations, US): Poxvirus
dilemmas -- monkeypox, smallpox, and biological terrorism.
(New England J. Med. 20 Aug 98 339:556)
QY: Joel G. Breman, Nat. Inst. of Health, Bethesda, MD 20892 US
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Summary by SCIENCE-WEEK  18Sep98

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

Related Background:

ALARM OVER AN OUTBREAK OF HUMAN MONKEYPOX DISEASE
The largest and most complex animal viruses are the poxviruses,
among them smallpox and a related virus called monkeypox.
Smallpox was ostensibly eradicated completely in 1979, and the
disease is more or less extinct, with debate now about whether to
completely extinguish the smallpox genome by destroying the last
of it in storage. Monkeypox, however, is far from eradicated.
Until recently the disease exhibited minor outbreaks, with the
incidence being quickly damped due to the apparent difficulty of
human to human transmission. In these outbreaks, the disease was
evidently transmitted by eating the meat of infected monkeys,
squirrels, and rats. Now, however, during the last year, there
has been a striking outbreak of 92 cases of monkeypox, all within
a few villages in the central part of the Democratic Republic of
Congo, and the most troubling aspect is the evidence that the
rate of human to human transmission may have suddenly increased
many-fold over what it has been in the past. Has the monkeypox
virus mutated to a more virulent form more easily transmitted
from one person to another? Medical epidemiologists are alarmed.
Peter Jahrling, a virologist at the U.S. Army Medical Research
Institute (MD US) says, "I hate to be accused of pushing the
alarmist button, but for practical purposes smallpox is back."
And Ali Khan, a medical epidemiologist at the U.S. Center for
Disease Control and Prevention, who recently visited the area of
the Congo in question, says, "I am personally concerned about
what would happen if this disease showed up in a major city." But
other virologists and epidemiologists, including some who
specialize in the poxviruses, are not convinced that human to
human transmission of monkeypox has actually increased
substantially. An argument can be made that the natural immunity
of the people of the Congo has been compromised by a high
incidence of HIV and the vicissitudes of armed conflict in the
area. The debate goes on, and the cases in the central Congo keep
mounting.
(Science 18 Jul 97) (Science-Week 29 Jul 97)


2. WHITE DWARF STARS AND GRAVITATIONAL MICROLENSING
Gravitational lensing is the bending of light and other radiation
by a massive gravitational entity such as a star, a black hole, a
galaxy, or a cluster of galaxies. The effect is predicted by
Einstein's theory of relativity and was first detected during a
total solar eclipse by Eddington in 1919. Large-scale
gravitational lensing causes multiple images of an object, the
type and arrangement of the images determined by the specifics of
the lensing entity. Gravitational "microlensing" is a small-scale
lensing effect, the gravitational field of the lensing object not
strong enough to form distinct images of the background source,
but instead causing an apparent brightening of the source. Stars
are expected to vary in brightness in a characteristic manner if
low-mass stars pass in front of them, and this effect has been
detected in the Large Magellanic Cloud and in the central bulge
of our Galaxy. The Magellanic Clouds are two comparatively small
and irregular galaxies close to our own galaxy, visible by the
naked-eye but observable only in the southern hemisphere, and
named after Ferdinand Magellan, who first recorded them in 1519.
The Large Magellanic Cloud has a diameter of approximately 10,000
*parsecs, and lies at a distance of approximately 50,000 parsecs
from Earth. The analysis of gravitational microlensing events of
stars in the Large Magellanic Cloud indicates the masses of the
lensing objects are in the range 0.3 to 0.8 solar-masses, which
suggests they might be old *white-dwarf stars. ... ... In an
analysis of white dwarf stars as possible sources of
gravitational microlensing events in the Large Magellanic Cloud,
Brad Hansen points out that 1) if white dwarfs exist in abundance
in the *halo of our Galaxy, this would apparently have profound
implications for our understanding of the early generations of
stars in the Universe; 2) previous attempts to theoretically
constrain the contribution of white dwarfs to microlensing
indicated they can account for only a small fraction of the
events, but these estimates relied on models of white dwarf
cooling that may be inadequate for the oldest white dwarfs. The
author presents cooling models proposed as appropriate for very
old white dwarfs, and using these models, the author reports that
the widely held idea that old white dwarfs are red applies only
to those with a helium atmosphere. Old white dwarfs with hydrogen
atmospheres, which could be a considerable fraction of the total
population of old white dwarfs, will appear blue, with colors
similar to those of the faint blue sources in the *Hubble Deep
Field. The author suggests that observational searches for the
population of microlensing objects should therefore look for
faint blue objects, rather than for faint red objects.
-----------
Brad M.S. Hansen (University of Toronto, CA): Old and blue white-
dwarf stars as a detectable source of microlensing events.
(Nature 27 Aug 98 394:860) 
QY: Brad M.S. Hansen 
-----------

Text Notes:
... ... *parsecs: 1 parsec equals 3.262 light-years, or 30.86 x
10^(12) kilometers.
... ... *white-dwarf stars: These are extremely dense and compact
stars that have undergone gravitational collapse after nuclear
fusion burn-out in their centers. They are the final stage in the
evolution of low-mass stars after such stars have lost their
outer layers. The white dwarfs are about the size of Earth, but
with a mass about that of the Sun.
... ... *halo: A galactic halo, such as that associated with our
own Galaxy, is a spheroidal distribution of old stars and
globular clusters of old stars surrounding the galaxy. In the
case of our own Galaxy, the galactic halo has a radius of
approximately 50,000 light years.
... ... *Hubble Deep Field: The orbiting Hubble Space Telescope
has the ability to discern images of galaxies too faint to be
picked up by planet-based and other orbital telescopes. After the
Hubble Space Telescope was repaired in 1993, one of the projects
begun with this instrument was the Hubble Deep Field Project,
which involves long-exposure detection of radiation received from
a relatively small area of the sky, the long-exposure providing
information concerning "deep" objects, i.e., objects extremely
distant from the instrument (in this case, beyond our local
Universe).
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Summary & Notes by SCIENCE-WEEK  18Sep98

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Related Background:

STUDY OF A PULSATING WHITE DWARF STAR
White dwarfs are the final phase in the evolution of low mass
stars. The stars from which they originate can be up to 8 solar
masses, but they lose 90% of their mass during star death, and
the remaining mass contracts until they have diameters only 1%
that of the sun. Most dead stars are white dwarfs, approximately
the size of the Earth, with masses approximately the mass of the
sun. This of course means an enormous density, 0.1 to 100 tons
per cubic centimeter, resulting from a terminal star the size and
mass of the sun collapsing to Earth-size. In a white dwarf, the
ordinary atomic structure has broken down completely, with
electrons and nuclei compacted tightly together by the gravitat-
ional force. The luminosity of white dwarfs is low, and they
gradually cool to become cold and dark objects. Many white dwarfs
have been identified, the first of them the dark companion of the
star Sirius. It is estimated that in our galaxy alone the number
of white dwarf stars is of the order of 10^(10). Don Winget et al
(University of Texas Austin, US; Universidade Federal do Rio do
Sul, BR) report that a study of the white dwarf star BPM 37093
indicates this particular pulsating white dwarf is massive enough
(about twice the white dwarf average) to have a crystalline
interior despite its apparent relatively high surface temperature
of over 11,000 degrees Celsius. But more evidence is needed to
sort out effects that could mimic indicators of crystallization,
and observations next year by the Hubble Space Telescope of this
star are planned.
QY: D. Winget, Univ. Texas Austin (512) 471-3350
(Astrophys. J. 1 Oct 97) (Science-Week 31 Oct 97)


3. EXPERIMENTAL EVIDENCE FOR MICROSCOPIC CHAOS
In the study of physical systems, the term "chaotic behavior" has
a specific meaning: the behavior of a system is said to be
"chaotic" if its final state is so sensitive to the system's
precise initial conditions that the behavior of the system is in
effect unpredictable and cannot be distinguished from a random
process, even though the behavior of the system is strictly
determinate in a mathematical sense. In other words, a
deterministic system characterized by extremely sensitive
instabilities, despite the system being determinate, can exhibit
behavior that is unpredictable, and the system is then called
"chaotic". During the past several decades, the analysis of such
chaotic systems has intrigued both physicists and mathematicians.
In general, in the study of physical systems, the term "phase
space" refers to a multidimensional space, each point of which
(phase point) completely represents the state of the system. For
example, in the study of dynamical systems, each phase point in
the phase space completely represents the values of all the
generalized coordinates and corresponding momenta. As the phase
point of a system moves in the phase space (e.g., changes with
time), the phase point follows a trajectory in the phase space,
and this trajectory is called the "phase point trajectory". In
the mathematical analysis of a particular phase space and its
phase point trajectories, "*Lyapunov exponents" are coefficients
that describe the rates at which nearby phase point trajectories
converge or diverge, and the Lyapunov exponents can be shown to
provide estimates of how long the behavior of a dynamical system
is predictable before chaotic behavior sets in. Chaotic behavior
of a system is characterized by the existence of positive
Lyapunov exponents. ... ... Gaspard et al present the results of
an experimental study of "microscopic chaos". The authors point
out that many macroscopic dynamical phenomena, for example in
hydrodynamics and oscillatory chemical reactions, have been
observed to display erratic or random time evolution, despite the
deterministic character of their dynamics -- a phenomenon known
as "macroscopic chaos". On the other hand, it has been long
supposed that the existence of chaotic behavior in the
microscopic motions of atoms and molecules in fluids or solids is
responsible for their equilibrium  and non-equilibrium
properties. But, the authors state, this hypothesis of
microscopic chaos has never been verified experimentally. The
authors now report direct experimental evidence for microscopic
chaos in fluid systems, the study involving the *observation of
brownian motion of a colloidal particle suspended in water. The
authors report finding a positive lower bound on the sum of
positive Lyapunov exponents of the system composed of the
brownian particle and the surrounding fluid. They suggest their
results and quantitative analysis provide strong experimental
evidence for microscopic chaos. They conclude: "On the assumption
that the system is deterministic, and given our knowledge of the
molecular structure of the fluid, this evidence supports, in
particular, the hypothesis that large systems -- which may be
treated by statistical mechanics -- are typically chaotic. The
result also supports the role of dynamical instability in non-
equilibrium fluids."
-----------
P. Gaspard et al (7 authors at 3 installations, BE US):
Experimental evidence for microscopic chaos.
(Nature 27 Aug 98 394:865)
QY: P. Gaspard 
-----------

Text Notes:
... ... *Lyapunov: A.M. Lyapunov (1857-1918) developed a general
theory of dynamic stability applicable to both linear and
nonlinear systems. His work was largely buried and forgotten
until it was exhumed nearly 30 years after his death.
... ... *observation of brownian motion: The experiment here
involved a colloidal particle of 2.5 microns diameter moving in
suspension in deionized water at 22 degrees Celsius, with
recorded observations of 145,612 positions over a total time
interval of approximately 2430 seconds, the observations
involving a microscope and video camera, the smallest resolution
stated as 25 nanometers. Particles of this size undergo
sedimentation, which may confound the results with non-Brownian
effects, but the authors report studies of non-sedimenting
smaller particles substantiate their observations, the larger
particle simply allowing tracking observations for a longer time.
-------------------
Summary & Notes by SCIENCE-WEEK  18Sep98


4. RESPONSE OF SINGLE DNA MOLECULES TO SUDDEN ELONGATIONAL FLOW
The theoretical study of the dynamics of flexible polymer
molecules in fluid flows has been an active area of research for
more than 60 years. A polymer in elongational flow begins to
deform when the force due to hydrodynamic friction across the
molecule exceeds the *entropic elasticity that tends to coil it.
Physical analysis of the dynamics may lead to an understanding of
the appearance of various polymer conformations. ... ... Smith
and Chu report a study in which individual fluorescence-labeled
*bacteriophage lambda-DNA molecules in sucrose and glucose
solutions were exposed to an elongational flow producing a high
*strain rate, and the dynamics of the molecules recorded with
video fluorescence microscopy. The flow was turned on suddenly so
that the entire evolution of molecular conformation could be
observed without initial perturbations. The rate of stretching of
individual molecules was highly variable and depended on the
molecular conformation that developed during stretching. This
variability is apparently due to a dependence of the dynamics on
the initial random equilibrium conformation of the polymer coil.
The authors suggest the increasing appearance at high strain 
rates of slowly unraveling hairpin folds is an example of
*nonergodic dynamics, which can occur when a statistical
mechanical system is subjected to *nonadiabatic (or "sudden")
external forces. The authors further suggest that nonequilibrium 
statistical mechanics may also play a role in the behavior of
large proteins when a local driving mechanism is faster than the
*relaxation times between different subunits of the protein.
-----------
D.E. Smith and S. Chu (Stanford University, US): Response of
flexible polymers to a sudden elongational flow.
(Science 28 Aug 98 281:1335)
QY: Steven Chu 
-----------

Text Notes:
... ... *entropic elasticity: In this context, elasticity is the
property whereby a molecule changes its shape due to imposed
forces, but recovers its original configuration when the forces
are removed. Entropic elasticity is an elasticity with an
equilibrium configuration governed by thermodynamic entropy
constraints.
... ... *bacteriophage lambda-DNA: Bacteriophage is a virus that
infects bacteria, the virus essentially consisting of a naked
strand of DNA surrounded by a complex polyhedral shell ("capsid")
composed mainly of glycoproteins. Lambda-DNA is DNA from the so-
called lambda type of bacteriophage.
... ... *strain: Strain is the deformation produced in a solid
(here a molecule) as the result of stress (external forces acting
on the system).
... ... *nonergodic dynamics: An ergodic system or process is one
in which averages computed from a data sample over time converge,
i.e., all sizeable data samples are equally representative of the
whole. In general, a dynamical system or process is ergodic if it
tends in probability to a limiting form which is independent of
the initial conditions. Nonergodic dynamics thus refers to
dynamics that never realize a limit independent of initial
conditions.
... ... *nonadiabatic: An adiabatic process is any thermodynamic
process, reversible or irreversible, that takes place in a system
without exchange of heat with the surroundings of the system. All
real processes are nonadiabatic in the sense that some heat
exchange always occurs. But close approximation to an adiabatic
ideal can be realized in practice.
... ... *relaxation times: The relaxation time of a system is a
measure of the time the system requires to return to equilibrium
(or assume a new equilibrium) after a sudden change in applied
forces, constraints, boundary conditions, etc. Also called the
time constant of the system. In a more general sense, the term
"relaxation time" is also used to describe the response time of a
system to any change in conditions.
-------------------
Summary & Notes by SCIENCE-WEEK  18Sep98


5. EVOLUTION: DINOFLAGELLATE ANCESTORS IN THE EARLY CAMBRIAN
*Dinoflagellates are single-celled organisms found in most
aquatic environments, and they form a major part of the modern
*plankton. Many *genera of dinoflagellates are sensitive to such
conditions as water salinity and nutrients, and some genera are
characteristic of latitudinal oceanic temperature zones. Thus,
the geographic distribution of dinoflagellates can be important
indicators of environmental conditions not only for present-day
environments but also for ancient environments. Fossilized
dinoflagellate cysts are widespread in *Mesozoic-Cenozoic
*sedimentary rocks, but ultrastructural data and molecular
phylogeny suggest they originated in the Neoproterozoic Era
(approximately 545 million years ago). ... ... Moldowan and
Talyzina report that an examination of dinoflagellate-specific
biological markers (dinosteranes and 4alpha-methyl-24-
ethylcholestane) in concentrated microfossils with known
morphology has resulted in the identification of ancient
dinoflagellate ancestors from the Early Cambrian (approximately
520 million years ago). The authors point out that fossilized
matter available for paleontological investigation represents
less than 1 percent of organisms that once existed on Earth, so
that a high abundance of related specimens in a particular age
suggests an earlier *radiation. They therefore suggest a
dinoflagellate ancestry originating in the Late Riphean
(approximately 800 million years ago).
-----------
J.M. Moldowan and N.M. Talyzina (2 installations, US SE):
Biogeochemical evidence for dinoflagellate ancestors in the Early
Cambrian. (Science 21 Aug 98 281:1168)
QY: J. Michael Moldowan, Stanford University 415-723-3058
-----------

Text Notes:
... ... *Dinoflagellates: These organisms are less than 1
millimeter in size. They have been classified as both plants and
animals, since some species contain chlorophyll. They have
flagella that provide them with locomotion, and they move in
response to light.
... ... *plankton: This is a general designation for various
drifting microscopic aquatic organisms in the upper regions of
the oceans, both photosynthetic and non-photosynthetic.
... ... *genera: In taxonomy, a genus is a collection of similar
species.
... ... *Mesozoic-Cenozoic: The Mesozoic Era refers to the time-
frame 65 to 245 million years ago; the Cenozoic Era refers to the
time-frame from the present to 65 million years ago.
... ... *sedimentary rocks: These are rocks formed by the
hardening of accumulated particles (sediments) that were
transported by agents such as wind and water. Such rocks are the
prime source of fossils.
... ... *radiation: In this context, the term "radiation" refers
to the spread of a group of biological entities into new
environments with consequent diversification.
-------------------
Summary & Notes by SCIENCE-WEEK  18Sep98


6. EVOLUTION: CLAY MINERAL VARIATION IN BURGESS SHALE FOSSILS
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.
Given the importance of the Burgess Shale, an understanding of
the mode of preservation of the soft-bodied fossils is a
prerequisite for interpretations of their morphology. At the
present time, however, the mode of preservation of Burgess Shale-
type fossils has remained unresolved. There are two current
models of Burgess Shale soft-body fossil preservation, one model
involving mechanisms for the preservation of organic carbon, and
the other model involving gel (clay sediment) stabilization of
soft tissue outlines, followed by compression and cementation.
... ... Orr et al report that chemical element mapping of Burgess
Shale fossils demonstrates that the relative abundance of
chemical elements varies between different anatomical features of
the specimens. The authors suggest these differences reflect the
compositions of the minerals that replicated the decaying
organism, with the different compositions controlled by
biological tissue chemistry. Since delicate morphological details
are replicated in the maps of chemical elements, the authors
suggest that *authigenic mineralization was fundamental to
preserving these fossils, even though some organic remains are
also present.
-----------
P.J. Orr et al (3 authors at University of Bristol, UK): Cambrian
Burgess Shale animals replicated in clay minerals.
(Science 21 Aug 98 281:1173)
QY: Patrick J. Orr, Dept. of Earth Sciences, University of
Oxford, Parks Road, Oxford QX1 3PR UK.
-----------

Text Notes:
... ... *Cambrian period: Refers to the time-frame 500 to 600
million years ago.
... ... *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.
... ... *authigenic mineralization: Authigenic minerals
(authigenes) are minerals that came into existence with or after
the formation of the rock of which they constitute a part.
-------------------
Summary & Notes by SCIENCE-WEEK  18Sep98


7. A NEW METHOD FOR FOLLOWING INDIVIDUAL CELLS IN SLIME MOLD
Dictyostelium discoideum is an organism that has been intriguing
biologists for most of this century. Although this organism is
often called a "cellular slime mold", it is not a mold and it is
not consistently slimy. A better common name for it is a "social
amoeba". What is most remarkable about the organism is its life
cycle. In one part of it life cycle, the "organism" consists of
individual dispersed amoebas living on decaying logs, eating
bacteria and reproducing by binary fission like most other
protozoans. Then, when the local food supply becomes exhausted,  
a rather astounding event occurs: tens of thousands of these
amoeba join together to form moving streams of cells that
converge at a central point, and there they aggregate to produce
a slug (grex) 2 to 4 millimeters long. The slug migrates as a
single body towards light, and when it reaches an illuminated
area, migration ceases, and the slug differentiates into a
fruiting body composed of spore cells and a stalk, the stalk
rising approximately 1 centimeter high above the plane of the
surface on which the slug has migrated. Inside the globular end
of the fruiting body, each spore cell is cellulose encapsulated.
In the denouement, the stalk cells die and the spore cells are
widely dispersed to become new amoeba, each of which will begin a
separate new population of cells both individual and social.
Thus, in this organism, initially identical cells are
differentiated into one of two alternative cell types, spore
cells and stalk cells. It is an organism where individual cells
come together to form a cohesive structure, aggregating into a
single organism, a quite remarkable feat of organization that
challenges biologists, chemists, and physicists. Much has been
learned about this organism in the past few decades, in
particular the apparent important role of release of cyclic
adenosine monophosphate (cAMP) in the initial aggregation that
produces the slug. ... ... J.T. Bonner (who has spent more than
50 years studying the social amoeba) points out that one of the
obstacles in studying D. discoideum is that it has been difficult
to follow the movements of individual cells within the slug. The
author now describes a new method for studying D. discoideum, the
method producing flat slugs one cell thick at a mineral oil-water
interface where one can follow the movement of all the cells. The
author reports that observations of time-lapse videos reveal the
following about slug migration: 1) While the posterior cells move
straight forward, the anterior cells swirl about rapidly in a
chaotic fashion. 2) Turning of the slug involves shifting the
high point of these hyperactive cells. 3) Both the anterior and
posterior cells move forward on their own power as the slug moves
forward. 4) There are no visible regular oscillations within the
slug. 5) The number of prestalk and prespore cells is
proportionate for a range of sizes of the mini-slugs involved in
these experiments (approximately 300 to 400 cells in each of
these mini-slugs). The author suggests that all of the
observations on thin slugs are consistent with observations of
normal 3-dimensional slugs, and that experiments with 2-
dimensional slugs may provide new insights into differentiation
and movements in this organism.
-----------
J.T. Bonner (Princeton University, US): A way of following
individual cells in the migrating slugs of Dictyostelium
discoideum. (Proc. Natl. Acad. Sci. US 4 Aug 98)
QY: J.T. Bonner, Princeton University 609-258-3000
-------------------
Summary by SCIENCE-WEEK  18Sep98


8. NEW EVIDENCE CONCERNING EVOLUTION OF THE IMMUNE SYSTEM
*Lymphocytes of the *vertebrate adaptive immune system rely on an
array of variable *immunoglobulin (antibody) and *T-cell *antigen
*receptors for specific recognition of antigens. In the genome,
the genes encoding the variable portions of these receptors are
typically split into variable components (V), joining components
(J), and in some cases, diversity gene components (D). One of
each type of each component or gene segment is joined together in
a site-specific *recombination reaction to form the *exon that
encodes the antigen-binding portion of the polypeptide that forms
the antibody or T-cell receptor. This reaction, known as V(D)J
recombination, occurs only in lymphocytes, and in some vertebrate
species is responsible for generating much of the diversity seen
in antigen receptors. It is known that the two proteins encoded
by the recombination-activating genes RAG1 and RAG2 are essential
to the V(D)J recombination reaction, the proteins mediating
sequence-specific DNA recognition of recombination "signals"
(specific short base-pair sequences involved in this particular
recombination process) and DNA cleavage next to these signals.
... ... Agrawal et al report that in vitro the proteins RAG1 and
RAG2 together form a *transposase capable of excising a piece of
DNA containing recombination signals from a donor site and
inserting the excised piece into a target DNA molecule. The
products formed contain a structure similar to that created by
*retroviral integration and by all known *transposition
reactions. The authors point out that all jawed vertebrates
studied thus far possess adjacent RAG1 and RAG2 genes as well
as immunoglobulin and T-cell receptor genes, which usually must
be assembled by *somatic recombination before they can be
expressed. There is no evidence that any of these molecules, or
antigen-specific lymphocytes, are found in jawless vertebrates
(hagfish and lamprey) or invertebrates. This indicates that split
antigen-receptor genes and the enzymatic machinery necessary for
their assembly into functional units arose in the approximately
100 million years between the divergence of jawless and jawed
vertebrates and the divergence of cartilaginous and bony fishes.
The authors suggest their results are evidence in favor of the
theory that a pivotal event in the evolution of the antigen-
specific immune system was the insertion of a "RAG *transposon"
into the genome of a vertebrate ancestor.
-----------
A. Agrawal et al (Yale University, US): Transposition mediated by
RAG1 and RAG2 and its implications for the evolution of the
immune system. (Nature 20 Aug 98 394:744)
QY: David G. Schatz 
-----------

Text Notes:
... ... *Lymphocytes: These are a type of leukocyte responsible
for the immune response. There are two classes of lymphocytes: 1)
the B-cells, which when presented with an activating chemical
entity (antigen) change into antibody producing plasma cells;
and, 2) the T-cells, which interact directly with foreign
invaders such as bacteria and viruses. There are also forms of T-
cells that are involved with B-cell activation.
... ... *vertebrate adaptive immune system: The term "adaptive"
here refers to those parts of the immune system that are capable
of adaptation to chemical experience.
... ... *immunoglobulin (antibody): In general, antibodies are
immunoglobulin proteins.
... ... *T-cell: see *Lymphocyte note above.
... ... *antigen: Any chemical entity that activates an immune
response, especially an entity originating outside the body.
... ... *receptors: In this context, cell surface macromolecules
that bind antigens.
... ... *recombination: In general, integration of DNA fragments
into a particular site in a genome.
... ... *exon: In general, any DNA sequence encoding and giving
rise to a translated polypeptide sequence.
... ... *transposase: Any enzyme required for the transposition
of DNA segments (see below, *transposition reactions).
... ... *retroviral integration: Retroviruses are single-stranded
RNA viruses that have an enzyme called reverse transcriptase,
and with this enzyme the viral RNA is used as a template to
produce viral DNA from cellular material. This DNA is then
incorporated (integrated) into the host cell's genome, where it
codes for the synthesis of viral components.
... ... *transposition reactions: In general, any reactions that
insert or excise DNA fragments into or from a genome.
... ... *somatic recombination: Somatic cells are any cells other
than germ cells (gametes). Somatic recombination, where it
occurs, involves the transposition of DNA fragments from one DNA
molecule to another, or within the same DNA molecule. Somatic
recombination theory is one of the theories proposed to explain
the enormous variety of antibodies produced by the immune system.
... ... *transposon: A large transposable genetic element having
at least the genes necessary for its own transposition to the
same or another genome.
-------------------
Summary & Notes by SCIENCE-WEEK  18Sep98

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

Related Background:

AN ANALYSIS OF HYPERMUTATION ANTIBODY GENE TARGETS
In vertebrates, the immune system provides protection against
foreign agents, for the most part by recognizing molecular
entities (antigens) that are interpreted by the immune system as
of foreign origin. Many types of cells are involved in the immune
response, with 3 primary types the so-called B-cells, cytotoxic
T-cells, and helper T-cells. In general, cytotoxic T-cells
recognize and kill host cells that are infected, while B-cells
are cells that secrete antibodies, protein molecules that bind to
antigens. Helper T-cells (and other immune system cells) are
involved in both processes, provoking particular steps in the
immune response. The ability of the immune system to recognize
and respond to the enormous number of antigens encountered by an
individual in a lifetime is due in large part to the diversity of
antibodies (also called *immunoglobulins) produced by B-cells.
Each B-cell produces only a single species of antibody, and
during the systemic immune response, the presence of a specific
antigen results in the proliferation by *clonal selection of
B-cells producing antibody specific for that antigen. All
antibody molecules are proteins consisting of two light
polypeptide chains and two heavy polypeptide chains that are
joined together by disulfide bonds. Each polypeptide chain
contains regions of variable amino acid sequence and regions of
constant amino acid sequence, resulting in an antigen-binding
locus with a variable specific affinity for particular ligands.
Further antibody variability arises from a variability in the way
the particular segments of the antibody are joined. The ability
of antibodies to recognize a large variety of antigens is thus
controlled, in part, by the variability of the variable segments
of the amino acid sequences of the antibody polypeptide chains.
This amino acid variability in the light and heavy chains is the
result of a variability in B-cell DNA generated by somatic
recombination, an alteration and reassembly of genes. During the
past 15 years, it has become evident that in immune system B-
cells, the part of the genome coding for the variable parts of
antibodies is involved in a process of "hypermutation", a
substantial increase in mutation rate, the effect of which is to
provide the immune system with a rapidly changing enormous
library of possible antibodies. This hypermutation process is
highly specific to the immune system, and it occurs only within a
DNA segment of approximately 1000 to 2000 DNA bases, the segment
that encodes the bulk of the variable regions of the antibody
polypeptides. The mechanism of the hypermutation process remains
unknown. ... ... Milstein et al (3 authors at Medical Research
Council, UK) report an analysis of the average frequency of
mutations of each of the 3 bases of all *nucleotide triplets in
the relevant DNA segment. Their focus was the question of whether
the B-cell hypermutation process involves one strand or both
strands of the DNA double helix. Many hypermutation models
propose that only one of the strands of DNA is involved in
hypermutation. The Milstein et al analysis used large databases
of mutations involving both variable and non-variable mutation
targets. The essential idea is that by using large databases of
such mutations, one can contrast the mutation distributions
observed with what would be expected if either one or both DNA
strands are hypermutation targets. The authors report their
analysis indicates there are two aspects of the hypermutation
process, one aspect that is DNA strand-dependent and the other
aspect that is not. The strand-independent aspect is sensitive to
local DNA sequences (i.e., mutation hot spots correlate with
local sequence environments), but without strand preference. The
authors report a similar conclusion has been reached by a
separate research group (Dorner et al, Immunol Rev. 162:161
1998).
QY: Cesar Milstein, Medical Research Council Laboratory of
Molecular Biology, MRC Centre, Hills Road, Cambridge CB2 2QH, UK.
(Proc. Natl. Acad. Sci. US 21 Jul 98 95:8791)
(Science-Week 21 Aug 98)

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

Related Background:

... ... *immunoglobulins: The immunoglobulins are a large
glycoprotein category that includes antibodies as a subset.
... ... *clonal selection: In this context, the process by which
an antigen selectively stimulates the proliferation of those
B-cells that possess antigen receptors targeted against the
stimulating antigen.
... ... *nucleotide triplets: Nucleotides are molecules
consisting a purine or pyrimidine base joined to a 5-carbon sugar
(ribose or deoxyribose) containing an attached phosphate group.
Nucleotides are the fundamental building blocks of nucleic acids,
and nucleotide triplets of 3 contiguous nucleotides are the
fundamental coding units of the genome.


9. ANALYSIS OF LATERAL DOMAINS IN CELL MEMBRANES
During the past 2 decades, a focus of research on biological cell
surface membranes (plasmalemmas) has been the lateral chemical
architecture. The fluid-mosaic model of cell membranes became the
consensus view in the 1970s, the idea essentially that the whole
structure has fluid properties resulting from rapid lateral
movement of most of its components through thermal agitation, the
rates of movement on the order of microns per second to microns
per minute. Since the molecules that constitute cell membranes
are quite diverse in size and chemical properties, any attempt to
understand the physiology and molecular biology of cell membranes
must consider the question of lateral organization. Lateral
heterogeneities in the classical fluid-mosaic model of cell
membranes are now thought of as domains or "rafts" comprising
clusterings of various lipids and *anchored proteins, these rafts
dictating the sorting of associated proteins and/or providing
sites for assembling cytoplasmic signaling molecules. However, at
present there is no direct evidence that rafts exist in living
cell membranes.  ... ... R. Varma and S. Mayor now report the use
of a special fluorescence microscopy technique (*fluorescence
resonance energy transfer microscopy) to measure lateral
heterogeneities in genetically engineered surface membranes of
cultured living cells (*CHO cells), with the focus of
investigation the distribution of a *folate-receptor isoform. The
authors report that glycosylphosphatidylinositol-anchored
proteins (*GPI-anchored protein) are clustered in domains that
are likely to be less than 70 nanometers in diameter, and these
domains are disrupted by removal of cellular cholesterol. The
authors suggest their results indicate that lipid-linked proteins
are organized in cholesterol-dependent submicron-size domains,
and that their methodology offers a new way of monitoring
nanometer-scale association between molecules in living cells.
... ... In a contiguous paper, T. Friedrichson and T.V.
Kurzchalia report the use of chemical crosslinking to demonstrate
that membrane microdomains of a GPI-anchored protein exist at the
surface in living cells (*MDCK cells and CHO cells), and this
clustering is specific for this GPI-anchored protein. Depletion
of membrane cholesterol causes disruption of the clustering,
whereas treatment of the cells with detergent substantially
increases the size of the complexes. The authors suggest that in
living cells these GPI-anchored proteins reside in microdomains
consisting of at least 15 molecules, these domains much smaller
than those seen after detergent extraction. They further suggest
that rafts are probably dynamic structures that are constantly
exchanging their components, and that the rules governing the
interplay between the inclusion and exclusion of proteins into
rafts remain to be defined.
-----------
R. Varman and S. Mayor (National Center for Biological Sciences
Bangalore, IN): GPI-anchored proteins are organized in submicron
domains at the cell surface. (Nature 20 Aug 98 394:798)
QY: Satyajit Mayor 
T. Friedrichson and T.V. Kurzchalia (Max Delbruck Center for
Molecular Medicine Berlin-Buch, DE): Microdomains of GPI-anchored
proteins in living cells revealed by crosslinking.
(Nature 20 Aug 98 394:802)
QY: Teymuras V. Kurzchalia 
-----------

Text Notes:
... ... *anchored proteins: The polypeptide chains of membrane
anchored proteins are situated outside the membrane bilayer, but
are covalently bound to lipid molecules inside the bilayer. Such
anchored proteins can protrude from either side of a membrane,
and in some cases the protein is a transmembrane entity, i.e.,
crosses the thickness of the bilayer.
... ... *fluorescence resonance energy transfer: This technique
has been previously used in the study of protein conformation in
solution. In the present report, the technique is coupled with
microscopy to visualize arrays of fluorescence domains on cell
surfaces.
... ... *CHO cells: A somatic cell line derived from Chinese
hamsters. The cells contain many chromosomes with deletions,
translocations, and aberrations.
... ... *folate-receptor isoform: An "isoform" is any one of
multiple forms of a functional protein that differ in amino acid
sequence and electrophoretic mobility. In this context, "folate"
is folic acid (vitamin B-9), an essential entity in biosynthesis.
The folate receptor protein complex is apparently transmembrane.
... ... *GPI-anchored protein: One of a diverse set of
(glyco)lipid-linked cell-surface proteins present in eukaryotic
cells (eukaryotic cells = cells with internal membrane 
compartments).
... ... *MDCK cells: A line of canine kidney cells.
-------------------
Summary & Notes by SCIENCE-WEEK  18Sep98


10. ON THE BACTERIUM STAPHYLOCOCCUS AUREUS
Staphylococci are *gram-positive bacteria that divide in planes
to produce clusters or packets. They are normally associated with
the skin and mucous membranes, and certain species are involved
in skin boils, abscesses, and carbuncles, especially if they
produce the enzyme coagulase, which causes blood clotting. The
species Staphylococcus aureus is involved in cases of food
poisoning, toxic shock syndrome, pneumonia, and staphylococcus
meningitis. Humans are apparently a natural reservoir of S.
aureus, with 30 to 50 percent of healthy adults occasionally
*colonized by these bacteria, and 20 percent persistently
colonized. ... ... F.D. Lowy presents a detailed review of the
current understanding of the pathogenesis, epidemiology, and
management of staphylococcal disease, and makes the following
points: 1) The staphylococcal genome consists of a circular
chromosome of approximately 2,800,000 nucleotide base pairs, and
additional extra-chromosomal *prophages, *plasmids, and
*transposons. Genes governing virulence and resistance to
antibiotics are found on the chromosome, as well as in the extra-
chromosomal entities. These genes are transferred between
staphylococcal strains, species, or other gram-positive bacterial
species through the extra-chromosomal entities. 2) The chemistry
and structure of the staphylococcal *cell wall have been
extensively analyzed. The cell wall consists of 50 percent
*peptidoglycan by weight, the peptidoglycan chains cross-linked
by tetrapeptide chains. Also present are ribotol techoic acids
and lipotechoic acid. 3) Staphylococcal membrane surface proteins
have also been extensively analyzed, and many of these proteins
have certain structural features in common, including positively
charged amino acids that extend into the cytoplasm, a hydrophobic
membrane-spanning domain, and a cell-wall anchoring region. 4)
Staphylococci produce numerous toxins that are grouped on the
basis of their mechanisms of action. Cytotoxins cause pore
formation in cells and induce *proinflammatory changes in
mammalian cells. The *pyrogenic-toxin *superantigens cause
extensive T-cell proliferation and *cytokine release. Enterotoxin
is responsible for toxic shock syndrome and food poisoning. 5)
Staphylococci produce various enzymes, such as *proteases,
*lipases, and *hyaluronidase, that destroy tissue. These
bacterial products may facilitate the spread of infection to
adjoining tissue, although their role in the pathogenesis of
disease is not clear. 6) Persons colonized with S. aureus are at
increased risk for subsequent infections. Rates of staphylococcal
colonization are high among patients with *type 1 diabetes,
intravenous drug users, patients undergoing hemodialysis, and
patients with AIDS. Patients with qualitative or quantitative
defects in *leukocyte function are also at risk. 7) More than 100
years after its first identification, S. aureus remains a
versatile and dangerous pathogen in humans, with frequencies of
both community-acquired and hospital-acquired staphylococcal
infections increasing steadily. At the present time, more than 95
percent of S. aureus isolates from humans are resistant to
penicillin, and resistance of S. aureus to antibiotic
alternatives is apparently increasing.
-----------
F. D. Lowy (Albert Einstein College of Medicine, US):
Staphylococcus aureus infections.
(New England J. Med. 20 Aug 98 339:520)
QY: Franklin D. Lowy, Department of Medicine, Montefiore Medical
Center, 111 E. 210th St., Bronx, NY 10467 US.
-----------

Text Notes:
... ... *gram-positive: Most bacteria can be classified into two
types, depending on the chemistry of their outer coat, which
chemistry determines whether a bacterium will admit certain dyes
into the interior. The classification, according to the
differential staining technique, is gram-negative vs. gram-
positive, named after the bacteriologist H.C. Gram (1853-1938).
Gram-positive bacteria take up a crystal violet stain and turn
purple, while gram-negative bacteria exclude the crystal violet
and counterstain instead with stains such as safranin, eosin red,
or brilliant green. As might be expected, since the technique
differentiates the outer coats of bacteria, some antibiotics are
effective against one type and not the other type, and vice
versa.
... ... *colonized: In this context, the term refers to
"carriers", i.e., humans carrying the pathogen without symptoms
of disease, who may or may not be at risk for later infections.
... ... *prophages: This is noninfectious bacteriophage DNA
integrated into a bacterial chromosome and multiplying with the
dividing bacterium.
... ... *plasmids: An extra-chromosomal piece of DNA, often
circular, mostly in bacteria but also in yeast, capable of
independent replication and also capable of translocation to
other organisms of the same or other species. Plasmids are
apparently involved in the transmission of antibiotic resistance
from one bacterial strain or species to another.
... ... *transposons: A transposon is a limited DNA sequence that
under the proper dynamic conditions can effectively translocate
from one DNA system to another, either in the same cell, or
between cells, or between cells of different organisms of the
same or different species, and remain functional.
 ... ... *cell wall: An extracellular coat of the cells of
bacteria, blue-green algae, plants, fungi, etc. The outer shell
of the S. aureus bacterium discussed in this report has 3 layers,
in order from the cytoplasm: cytoplasmic membrane (plasmalemma),
cell wall, and capsule. The cell wall consists primarily of
peptidoglycan (polysaccharide) polymer, while the capsule
consists primarily of a variable polysaccharide polymer. The
capsule layer, however, may not be present in some varieties.
... ... *peptidoglycan: This consists of alternating
polysaccharide subunits of N-acetylglucosamine and N-
acetylmuramic acid with 1,4-beta linkages.
... ... *proinflammatory: Inflammation is a complex cytological
and chemical response to injury by physical, chemical, or
biological agents, and the term "proinflammatory" here refers to
a cytological precursor stage of the inflammation process.
... ... *pyrogenic: Causing fever.
... ... *superantigens: A superantigen is an antigen that
interacts with the T-cell receptor in a domain outside of the
receptor's antigen recognition site. This type of interaction
induces the activation of large numbers of T-cells, the number
large compared to the number resulting from antigens binding at
the antigen recognition site.
... ... *cytokine: A cytokine is any substance that promotes cell
growth and cell division. Certain cytokines are endogenous, and
need to be controlled by cell regulatory mechanisms. When these
mechanisms fail, endogenous cytokines may be implicated in
serious human diseases such as rheumatoid arthritis, where
apparently deregulated cytokines cause the inflammatory response
that produces the symptoms. 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. 
... ... *protease: Any enzyme that hydrolyzes (degrades)
proteins, usually into component oligopeptides or amino acids
... ... *lipase: Any enzyme that splits lipid molecules.
... ... *hyaluronidase: An enzyme that hydrolyzes the
mucopolysaccharide hyaluronic acid. Hyaluronic acid forms a
gelatinous material in tissue spaces and generally acts as a
lubricant and shock absorbant.
... ... *type 1 diabetes: Insulin-dependent diabetes mellitus.
... ... *leukocyte: White blood cells.
-------------------
Summary & Notes by SCIENCE-WEEK  18Sep98