ScienceWeek

SCIENCE-WEEK

SCIENCE-WEEK - Part 1/3

A Free Weekly Digest of the News of Science

May 1, 1998 - Issue #53

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Science keeps moving us away from the Apes. Of course, if one
wants to be an ape, one objects to the movement.
-- The Editors
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Contents of This Issue:

Part 1:
1. A New US Feud Concerning Clinical Trials of an AIDS Vaccine
2. A Gravitational Diffusion Model Without Dark Matter
3. On the Formation of Star Clusters
4. On the Impact Hazards of Asteroids
5. A Method to Produce Protein Passage Through Cell Membranes
6. On the Movements of a Virus in a Plant

Part 2:
7. Role of Mouse Telomerase in Highly Proliferative Organs
8. A Marine Natural Product that Inhibits Kinesin Motors
9. On Chemokines and Leukocyte Traffic
10. Antagonistic Symbiosis: Abduction of One Species by Another

Part 3:
11. On the Curious Reproductive Tract of the Female Armadillo
12. On Viral Strategies of Immune Evasion
13. On Homeostasis and Self-Tolerance in the Immune System
14. On Natural and Engineered Disorders of Lymphocyte Development
15. Identification of a Gene for Juvenile Parkinsonism

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1. A NEW US FEUD CONCERNING CLINICAL TRIALS OF AN AIDS VACCINE
Jonathan Mann (Allegheny University, US), the former director of
the World Health Organization Global Program on AIDS, has accused
the US National Institutes of Health of violating human rights by
not proceeding to large-scale clinical trials of AIDS vaccines.
The remarks were apparently made last month in an address to the
Presidential Advisory Council on AIDS. Officials at NIH say the
remarks by Mann are uninformed and unnecessarily inject politics
into what should be a rational scientific debate. Gregg
Gonsalves, a spokesman for the Treatment Action Group, a national
AIDS research advocacy organization, has called Mann's remarks
"outrageous and irresponsible".
(Nature 9 Apr 98) (Science-Week 1 May 98)


2. A GRAVITATIONAL DIFFUSION MODEL WITHOUT DARK MATTER
R.J. Britten (California Institute of Technology, US) presents a
model that without dark matter quantitatively describes the flat
rotation curves of galaxies and the mass-to-light ratios of
clusters of galaxies. The hypothesis is that the agent of
gravitational force is propagated as if it were scattered with a
mean free path of about 5 kiloparsecs. As a result, the force
between moderately distant masses separated by more than the mean
free path diminishes as the inverse first power of the distance,
following diffusion equations, and describes the flat rotation
curves of galaxies. The force between masses separated by EMAIL
(Proc. Natl. Acad. Sci. US 31 Mar 98 95:3351)
(Science-Week 1 May 98)

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Related Background:

ON THE AGGREGATION OF YOUNG GALAXIES IN A DARK-MATTER UNIVERSE
The term "semi-analytic modeling" refers to a quantitative
modeling procedure in which empirical data are used in places to
fix the values of parameters or functions, rather than deriving
these from theoretical principles. N-body simulations, which
usually require extraordinary computational resources, are
simulations involving calculations of interactions of a large
population of entities. "Dark matter", which is thought to
comprise as much as 90% or more of the mass of the universe, is
undetectable except by gravitational effects, and "cold dark
matter" refers to dark matter particles created with low velocity
dispersions in the early universe. At the present time, computer
simulations and empirical observations of galaxy clustering favor
the idea that most dark matter in the universe is cold dark
matter. ... ... Governato et al (7 authors at 3 installations, UK
DK US) report the use of a combination of theoretical techniques
(semianalytic modeling and n-body simulations) to show that large
concentrations of young galaxies (i.e., galaxies in existence
when the universe was one-tenth of its current age) should be
quite common in a universe dominated by cold dark matter, and
that such galaxy concentrations are the progenitors of the rich
galaxy clusters seen today. The authors suggest these clustering
properties of primeval galaxies will be compared with data
collected in the near future, and that the comparison will be a
test of our current understanding of galaxy formation within the
framework of a universe dominated by cold dark matter.
QY: C.S. Frenk (c.s.frenk@durham.ac.uk)
EMAIL
(Nature 26 Mar 98) (Science-Week 10 Apr 98)


3. ON THE FORMATION OF STAR CLUSTERS
Elmegreen and Efremov (2 installations, US RU) review current
views concerning the formation of star clusters. Star clusters in
a spiral galaxy such as the Milky Way are found in the halo and
the disk. The Milky Way's halo contains about 200 globular
clusters that appear to be as old as the Galaxy itself
(approximately 13 billion years). In contrast, the Galactic disk
contains younger star groups arranged in open clusters,
associations, and complexes. The authors suggest that all star
clusters, regardless of age and appearance, can be explained by
the same basic mechanism: the structuring of star-forming gas
into a hierarchical distribution of clouds by the actions of
turbulence and gravity. A third influence is involved in
"triggered" star formation, a mode of star birth that follows the
direct compression of gas by an outside source such as hot young
stars or supernovas. These outside sources can move gas around,
leading to the formation of new gas clouds out of low-density
material, or to fast collapse and star formation inside pre-
existing clouds. Many examples of apparent triggered star
formation exist in our Galaxy and other nearby galaxies.
QY: Bruce Elmegreen, IBM T.J. Watson Research Cntr, PO Box 218,
Yorktown Heights, NY US.
(American Scientist May/Jun 1998) (Science-Week 1 May 98)

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Related Background:

ON THE BIRTH OF STAR CLUSTERS
A star cluster is a group of stars whose members are close enough
to each other to be physically associated, and the current
consensus is that the stars in a cluster formed together. A
globular cluster is a spherically symmetrical and compact cluster
of stars, the cluster containing from several tens of thousands
to perhaps a million stars, and as in clusters in general, these
stars are thought to share a common origin. The Hubble Space
Telescope, named after the astronomer Edwin Hubble (1889-1953),
was launched from a space shuttle in 1990 into a 600-kilometer
low-Earth orbit and has been providing extensive imaging and
spectroscopic observations critical for the development of
astronomy and astrophysics. The new information has concerned hot
stars, stellar chromospheres and coronas, the interstellar
medium, galaxies and galactic clusters, quasars, etc. -- all of
it information uncorrupted by the Earth's atmosphere, which is
the problem for ground based telescopes. ... ... Meylan and
Brandl (2 installations, DE US), in a review of the birth of star
clusters, focus on the nebula NGC 2070 (also known as 30 Doradus
or the "Tarantula Nebula"), and note that it is now known that
this nebula in the nearby galaxy called the Large Magellanic
Cloud is an exceptionally massive and luminous concentration of
ionized hydrogen (showing an "H II" region in the spectrum) where
thousands of stars are in the process of being born, and that
recent observations by the Hubble Space Telescope indicate that
in NGC 2070 the birth of a globular star cluster may be
occurring. QY: Georges Meylan, European Southern Observatory,
Garching DE (Sky & Telescope March 1998) (Science-Week 30 Jan 98)


4. ON THE IMPACT HAZARDS OF ASTEROIDS
G. Verschuur (University of Memphis, US) reviews the
probabilities and consequences of asteroid collisions with Earth.
Our civilization has just passed through an extraordinary era of
scientific discovery that has brought with it the awareness that
planet Earth is profoundly vulnerable to devastating cosmic
collisions. In recent years, the evidence that mass extinctions
of life on Earth can be attributed to the consequences of comet
or asteroid impacts has become overwhelming. Most famous among
such catastrophes is the Cretaceous-Tertiary impact that
apparently marked the demise of the dinosaurs about 65 million
years ago. The attention of many planetary scientists has turned
to the problem of assessing the likelihood that our civilization
may be threatened by a rogue comet or asteroid in the near
future. Asteroid hunters estimate that 9000 objects of dimensions
0.5 kilometers or larger are in near-Earth orbits, and that of
these only 350 have been identified to date. A small-to-medium
size 200 meter object smashing into a 5-km deep ocean at 50 km
per second would raise a splash 35 kilometers high in 40 seconds
and produce tsunamis that would inundate lands bordering the
ocean. Calculations indicate that the impact anywhere on Earth of
even a medium-size asteroid 0.2 to 1.0 km would be catastrophic.
The author suggest that we have been lucky to avoid a recent 
catastrophic collision with a comet or asteroid, and that
although it may not happen in the next year or the next century,
eventually the Earth *will* be hit by a sizable piece of cosmic
debris. QY: Gerrit L. Verschuur, Univ. of Memphis 901-678-2169.
(Sky & Telescope June 1998) (Science-Week 1 May 98)


5. A METHOD TO PRODUCE PROTEIN PASSAGE THROUGH CELL MEMBRANES
Cell membranes are generally resistant to permeation by large
molecules such as peptides and proteins. Since certain large
molecules can be effective agents for interacting with cellular
control mechanisms, methods of effecting the permeation of large
molecules are of considerable significance. ... ... Lin et al (4
authors at Vanderbilt University, US) report that entire proteins
can be moved through cell membranes by fusing their C-terminals
to a 12-amino-acid membrane translocating sequence. Glutathione
S-transferase fusion proteins as large as 45 kilodaltons were
moved into living cells, and a permeated fusion protein including
a signal transduction protein fragment retained biological
activity once inside. The authors suggest their protein delivery 
technique should be useful for intracellular functional studies,
and drug and vaccine development.
QY: Yao-Zhong Lin, Vanderbilt University, Dept. of Microbiology,
615-322-7311
(Nature Biotechnology 16:370 1998) (Chem. & Eng. News 13 Apr 98)
(Science-Week 1 May 98)


6. ON THE MOVEMENTS OF A VIRUS IN A PLANT
To achieve systemic infection, plant viruses move from cell to
cell and over long distances by exploiting the transport
mechanisms for macromolecules within the host plant. But less is
known about translocation of viruses throughout the plant than
about cell-to-cell movement. To achieve long distance movement,
plant viruses enter the vascular system (phloem and/or xylem),
move within, and exit the vasculature at some distal point.
However, the mechanisms of loading and unloading of viruses
within conducting elements (sieve tubes and xylem vessels) and
their migration to surrounding cells is poorly understood.
... ... Opalka et al (7 authors at 2 installations, US FR) report
a study of rice yellow mottle virus in tissues of inoculated and
systematically infected rice plants (Oryza sativa L.), the
procedure involving Western immunoblotting, Northern blotting,
and thin-section electron microscopy. From their results, the
authors propose that the partial digestion of pit membranes
resulting from programmed cell death (apoptosis) may permit virus
migration concomitant with autolysis, and that displacement of
calcium ion from pit membranes to virus particles may contribute
to the disruption of the pit membranes and facilitate systemic
virus transport.
QY: Mark Yeager (yeager@scripps.edu)
EMAIL
(Proc. Natl. Acad. Sci. US 17 Mar 98 v95:p3323)
(Science-Week 1 May 98)

(continued in Part 2)

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SCIENCE-WEEK - Part 2/3

A Free Weekly Digest of the News of Science

May 1, 1998

Contents of Part 2:

7. Role of Mouse Telomerase in Highly Proliferative Organs
8. A Marine Natural Product that Inhibits Kinesin Motors
9. On Chemokines and Leukocyte Traffic
10. Antagonistic Symbiosis: Abduction of One Species by Another

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7. ROLE OF MOUSE TELOMERASE IN HIGHLY PROLIFERATIVE ORGANS
Telomeres are guanine-rich repeat sequences that form the
physical ends of the chromosomes of cells containing membrane-
bound organelles, and there is evidence these terminal structures
may be important in chromosome function. Synthesis and
maintenance of telomeric repeats are mediated by the specialized
ribonucleoprotein complex "telomerase". ... ... Lee et al (6
authors at 4 installations, US ES) report a study of the role of
the enzyme telomerase in highly proliferative organs in
successive generations of mice lacking telomerase RNA. Late
generation animals exhibited defective spermatogenesis, with
increased programmed cell death (apoptosis) and decreased
proliferation in the testis. The proliferative capacity of
hematopoietic cells in bone marrow and spleen was also
compromised. These progressively adverse effects coincided with
substantial erosion of telomeres and fusion and loss of
chromosomes. The authors suggest their findings indicate an
essential role for telomerase, and hence telomeres, in the
maintenance of genomic integrity and in the long-term viability
of high-renewal organ systems. They also suggest that the high
proliferation index of most cancer cells compared with the more
sporadic cycling of normal stem-cell populations indicates that
telomerase inhibition should be well tolerated in clinical
settings. QY: Ronald A. DePinho, Albert Einstein College of
Medicine 718-430-2106.
(Nature 9 Apr 98 392:569) (Science-Week 1 May 98)

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Related Background:

EXTENSION OF MITOTIC LIMITS BY TELOMERASE EXPRESSION
Somatic cells are all cells other than germline cells such as egg
cells and sperm cells, and the term "cellular replicative
senescence" refers to the observation that somatic cells, in
contrast to germline cells, can proliferate (divide) only a fixed
number of times, the actual number dependent on the organism from
which the somatic cells derive. Since there is a general correl-
ation between cellular replicative senescence in vitro and the
average life-spans of various animals (including humans),
cellular replicative senescence has been implicated in aging and
age-related pathologies. Telomeres are regions at the ends of
chromosomes consisting of repeats of particular nucleotide
sequences, and with each somatic cell division a small part of
the telomere is ordinarily lost. What has been observed is that
in germline cells the lengths of telomeres are maintained
constant by repair, while in somatic cells this repair does not
occur, and this difference has led to the idea that the finite
proliferative capacity of somatic cells is related to the
ultimate depletion of telomere lengths. The enzyme telomerase is
the enzyme that causes repair of telomeres, and this enzyme is
active in germline cells, but it is not expressed in most somatic
cells. 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, and fibroblasts are a type
of connective tissue cell that secret structured proteins such as
collagen. Transfection is the uptake of exogenous (foreign) DNA
fragments in solution directly into animals cells in laboratory
culture, and is one method of introducing foreign genes into
cells. The term "vector", in the context of DNA cloning, is any
DNA fragment used in a transfection process. ... ... Bodnar et al
(10 authors at 2 installations, US) now report that two normal
human cell types (retinal pigment epithelial cells and foreskin
fibroblasts) that do not ordinarily express telomerase, can be
transfected with vectors encoding the human telomerase catalytic
subunit, the transfected cells (as opposed to controls) then
exhibiting elongated telomeres, dividing vigorously and exceeding
their normal life-span by at least 20 doublings. The authors
suggest their results establish a causal relationship between
telomere shortening and in vitro cellular replicative senescence,
and that the ability to maintain normal human cells in a youthful
state can have important applications in research and medicine.
QY: Serge Lichtsteiner 
(Science 16 Jan 98) (Science-Week 30 Jan 98)

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Related Background:

NEW DATA AGAINST IMPORTANT TELOMERASE ROLE IN CANCER
Telomeres are defined ends of chromosomes that contain specific
repeated DNA sequences. They are essential for normal chromosome
replication, and since their length shortens a bit with each
replication, they are believed to be involved in the aging of the
cell. Telomerase is an enzyme that repairs damage to telomeres,
and it is thought by some that cancerous cells may have mutant
telomerase, the mutant enzyme conferring immortality on the
cancer cell. Now M. A. Blasco et al (Cell 91:25 1997) have
genetically engineered telomerase-deficient mice and have shown
that after 6 generations these mice are both viable and fertile.
Commenting on this research, David Wynford-Thomas and David
Kipling (University of Wales College of Medicine, Cardiff UK)
suggest that telomerase inhibitors that have been envisaged for
cancer therapy will therefore not have any acute toxicity against
cancer cells or other cells. Blasco et al have suggested that
current dogma that telomerase facilitates tumor growth may be
wrong, with telomerase nothing more than a "passive bystander" in
oncogenesis. (Nature 9 Oct 97) (Science-Week 24 Oct 97)


8. A MARINE NATURAL PRODUCT THAT INHIBITS KINESIN MOTORS
Eukaryotic cells depend on dynamic microtubule-mediated events
executed by members of the kinesin superfamily of proteins.
Various kinesins are necessary for cell division, and for vesicle
and organelle transport. More than 100 kinesin superfamily
members have been identified, with different kinesins sharing a
common 350-amino acid motor domain, which is necessary and
sufficient for ATP force generation, and this motor domain is
attached to a variety of cargo-binding or effector tail domains.
... ... Sakowicz et al (7 authors at University of California San
Diego, US) report the isolation from a marine sponge (Haliclona,
also known as Adocia) species of adociasulfate-2, a compound
that
inhibits kinesin activity by targeting the kinesin motor domain
and mimicking the activity of the microtubule. The authors
suggest the kinesin-microtubule interaction site could be a
useful target for small molecule modulators, and that adocia-
sulfate-2 can serve as an archetype for specific inhibitors of
kinesin functions.
QY: Lawrence S.B. Goldstein (lgoldstein@ucsd.edu)
EMAIL
(Science 10 Apr 98) (Science-Week 1 May 98)

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Related Background:

MOTOR PROTEINS AND ORGANELLE TRANSPORT
The interior of a living cell is a dynamic system involving a
dynamic supporting matrix, active synthesis and degradation of a
variety of small and large molecules, and the regulated transport
of various molecular species to local and remote sites within the
cell. Research during the past two decades has provided revel-
ations concerning the molecular biology of a variety of orchestr-
ated movements with the cell interior, particularly movements
producing the transport of cell organelles (organized subsyst-
ems). "Motor proteins" are mechanico-chemical enzymes involved in
locomotion or transport, and there are three families of such
proteins: kinesins, dyneins, and myosins. Kinesins and dyneins
are microtubule based motor proteins, while myosin is a micro-
filament based motor protein. In general, as mechanico-chemical
enzymes, motor proteins convert energy from hydrolysis of nucleo-
tides to mechanical force, and since they are involved in many
important cellular events, the molecular details are currently
the focus of intensive research. ... ... N. Hirokawa (University
of Tokyo, JP) reviews the molecular mechanisms of organelle
transport in cells, particularly the role of the motor proteins
kinesin and dynein. The author suggests that in the near future
we will fully understand how the cell sorts and transports
proteins and lipids to their appropriate intracellular
destinations. QY: Nobutaka Hirokawa 
(Science 23 Jan 98) (Science-Week 6 Feb 98)

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

Related Background:

INDUCED REVERSAL OF KINESIN MOTION IN CELLS
Microtubules are part of the cytoskeleton of biological cells,
the quasi-rigid matrix that among other things determines cell
shape. The microtubules are 25 nanometers in diameter, and
composed of the protein tubulin. They occur in regular arrays in
cilia, flagella, the mitotic spindle, and in the cytoplasm in
general, and they contribute not only to cell shape, but also to
cell motility. In the neuron axon, for example, the microtubules
are the rails along which material is transported in one
direction or another over long distances. Microtubules have
directionality, in the sense that the two ends apparently differ
chemically, and the difference can be recognized by certain cell
constituents. According to their organization in the cell, the
ends of the microtubules are labelled as plus or minus. Kinesin
is one of a family of motor proteins associated with micro-
tubules, the kinesin molecules able to move organelles and
particles toward one end of microtubules using energy derived
from adenosine triphosphate (ATP) hydrolysis. There are several
types of kinesin, and each type moves material in one direction
only, either toward the plus end of the microtubule or toward the
minus end of the microtubule. As far as its structure is con-
cerned, the protein kinesin apparently consists of two light
chains and two heavy chains combined to form a long thin molecule
with two globular heads at one end, with each of the globular
heads containing an ATP binding site. After the kinesin attaches
to an organelle that is to be transported, the head groups of the
kinesin molecule, by some means, "walk" along the surface of a
microtubule using energy from ATP hydrolysis. The head groups are
called the "motor domain", since they are evidently involved in
the movement process. Last week Ulrike Henningsen and Manfred
Schliwa (University of Munich, DE) reported what is being called
a remarkable experiment concerning kinesin. Essentially, what
they did is take two types of kinesin, one type that walks to the
plus end of microtubules, and another type that walks to the
minus end of the same microtubules, and using genetic engineering
methods, they produced a chimera, a new kinesin molecule with the
head of the minus walker and the tail of the plus walker, and
they demonstrated that the direction of movement of the kinesin
heads (the motor domains) were reversed by the tail substitut-
ions. This is a surprising result, and it has evidently caused
some excitement among biologists.
QY: M. Schliwa 
(Nature 4 Sep 97) (Science-Week 19 Sep 97)


9. ON CHEMOKINES AND LEUKOCYTE TRAFFIC
There is intense interest among immunologists and virologists in
chemokines, which are immune system signaling molecules. The
receptors for chemokines are proteins on the surfaces of cells,
and there is evidence that HIV uses these receptors to force
entry into immune system T-cells. Leukocytes are white blood
cells, immune system cells that migrate to tissues as part of the
immune response. ... ... M. Baggiolini (University of Bern, CH)
reviews the control of leukocyte traffic by chemokines. Over the
past 10 years, numerous chemokines have been identified as
attractants of different types of blood leukocytes to sites of
infection and inflammation. Chemokines are produced locally in
tissues and act upon leukocytes through selective receptors, and
the chemokines are now known to also function as regulatory
molecules in leukocyte maturation, in traffic and homing of
lymphocytes, and in the development of lymphoid tissues. A more
speculative issue is the possible role of chemokines in bringing
or keeping together cells that form a functional unit. A
potential role of chemokines in morphogenesis is possible.
QY: Marco Baggiolini, Theodor Kocher Inst., Univ. of Bern, PO Box
CH-3000, Bern 9, CH.
(Nature 9 Apr 98 392:565) (Science-Week 1 May 98)


10. ANTAGONISTIC SYMBIOSIS: ABDUCTION OF ONE SPECIES BY ANOTHER
McClintock and Baker (2 installations, US) review chemical
ecology in antarctic seas. Many interactions between species
occur on a covert level and are difficult to perceive. These
interactions are chemical, not physical, and rely on substances
such as pheromones that attract mates, as well as toxins that
repel or kill predators, competitors, and other enemies. Chemical
interactions can profoundly alter the conventional scenarios
posited by ecologists studying predators and their prey. The
research of the authors has focused on secondary metabolites,
chemicals that do not seem to be required for any of the primary
metabolic processes such as energy production, respiration, or
photosynthesis. They have found that sessile and sluggish
organisms on the antarctic ocean floor are much threatened by
invertebrate predators and competitors, and the threatened
organisms have developed chemical defenses to ward off their
enemies. In one unusual adaptation, the amphipod crustacean
Hyperiella dilatata captures the sea butterfly Clione antarctica
(a snail without a shell). The sea butterfly is held alive in a
sustained forced attachment on the back of the crustacean, and
experiments and analysis reveal that the sea butterfly secretes a
previously undescribed beta-hydroxyketone that turns away fish
that are normally predators of the crustacean. The authors
suggest this unique association -- the abduction of one species
by another -- is unprecedented in the annals of behavioral and
chemical ecology.
QY: James B. McClintock (mcclinto@uab.edu)
EMAIL
(American Scientist May/Jun 1998) (Science-Week 1 May 98)

(continued in Part 3)

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

SCIENCE-WEEK - Part 3/3

A Free Weekly Digest of the News of Science

May 1, 1998

Contents of Part 3:

11. On the Curious Reproductive Tract of the Female Armadillo
12. On Viral Strategies of Immune Evasion
13. On Homeostasis and Self-Tolerance in the Immune System
14. On Natural and Engineered Disorders of Lymphocyte Development
15. Identification of a Gene for Juvenile Parkinsonism

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11. ON THE CURIOUS REPRODUCTIVE TRACT OF THE FEMALE ARMADILLO
Loughry et al (4 authors at 3 installations, US IE) review
polyembryony in armadillos. Polyembryony is a form of
reproduction in which one sexually reproduced embryo splits into
two or more embryos. Many animals, including humans, are
occasionally polyembryonic (the birth of identical twins,
triplets, etc.). It is the norm in certain animal types such as
parasitic wasps, certain flatworms, and various aquatic
invertebrates. But among invertebrates, only the 6 species of
armadillos in the genus Dasypus are always polyembryonic. In the
nine-banded armadillo, which is the best studied, females
typically give birth to litters of genetically identical
quadruplets. The authors report their research concerning the
nine-banded armadillo has revealed that an unusual characteristic
of the reproductive tract of the female may have promoted the
evolution of polyembryony in this species. These armadillos have
a uniquely shaped uterus with such a small implantation site that
it can accommodate only one blastocyst. The authors suggest that
polyembryony may have evolved in these animals to bypass that
constraint and increase reproductive success. The authors further
suggest that their study of armadillos indicates the production
of clonal offspring by nine-banded armadillos has had little
apparent impact on their behavior or ecology, a consideration
that may be of significance in evaluating the ramifications of
artificial animal cloning.
QY: W.J. Loughry (jloughry@valdosta.edu)
EMAIL
(American Scientist May/Jun 1998) (Science-Week 1 May 98)


12. ON VIRAL STRATEGIES OF IMMUNE EVASION
H.L. Ploegh (Harvard University, US) reviews the mechanisms used
by viruses to subvert normal host defenses. The vertebrate body
is an ideal breeding ground for viruses and provides the
conditions that promote their growth, survival, and transmission.
The vertebrate immune system is an evolved system and it deals
with this challenge. Since, mutually assured destruction is not a
viable evolutionary strategy, the study of host-virus
interactions provides not only a glimpse of life at immunity's
edge, but it has also illuminated essential functions of the
immune system, in particular the area of major histocompatibility
complex-restricted antigen presentation. The author suggests that
although the emergence of new viral diseases is a constant
reminder that viral pathogens are usually one-step ahead of the
host, the study of viral immune evasion helps to close that gap.
QY: Hidde L. Ploegh, Harvard Univ. Medical School 617-432-1550.
(Science 10 Apr 98 280:248) (Science-Week 1 May 98)


13. ON HOMEOSTASIS AND SELF-TOLERANCE IN THE IMMUNE SYSTEM
Parijs and Abbas (Harvard University, US) review the principal
control mechanisms for 1) maintaining homeostasis after active
immune responses to foreign antigens; and, 2) preventing or
aborting responses to self-antigens. The immune system responds
in a regulated fashion to microbes and eliminates them, but it
does not respond to self-antigens. Several regulatory mechanisms
function to 1) terminate responses to foreign antigens, returning
the immune system to a basal state after the antigen has been
cleared; and 2) maintain unresponsiveness or tolerance to self-
antigens. In this review, the emphasis of the authors is on T
lymphocytes, since many of the recent advances have come from
studies of T cells, but the authors propose it is likely that the
general principles are applicable to all lymphocytes. The authors
suggest that elucidating the nature of these homeostatic
mechanisms may lead to better strategies for suppressing harmful
immune responses, and for augmenting and sustaining beneficial
responses to microbial vaccines and tumors.
QY: Abul K. Abbas, Harvard Univ. Medical School 617-432-1550.
(Science 10 Apr 98 280:243) (Science-Week 1 May 98)


14. ON NATURAL AND ENGINEERED DISORDERS OF LYMPHOCYTE DEVELOPMENT
Fischer and Malissen (2 installations, FR) review the natural and
engineered mutations that perturb normal T and B cell development
in primary lymphoid organs. Mammals have evolved complex
developmental pathways to generate a large repertoire of B and T
cell lymphocytes capable of mounting effective immune responses.
Analysis of natural and engineered immunodeficiencies constitutes
a powerful approach to delineating these pathways and identifying
the molecular sensors that couple the survival of developing
lymphocytes to the achievement of successful gene rearrangements
at the loci coding for B and T cell antigen receptors. The
authors suggest that besides identifying cytokines, growth
factors, and transcription factors involved in lymphocyte
development, genetic analysis also makes it possible to organize
most of these protagonists into gene networks that control
critical events in the life of developing lymphocytes.
QY: Bernard Malissen, INSERM-CNRS de Marseille-Luminy, FR
(Science 10 Apr 98 280:237) (Science-Week 1 May 98)


15. IDENTIFICATION OF A GENE FOR JUVENILE PARKINSONISM
Parkinson's disease is a common neurodegenerative disease with
complex clinical features. Autosomal recessive juvenile
parkinsonism has been related to the long arm of chromosome 6 and
to several genetic markers. Kitada et al (9 authors at 4
installations, JP) report the identification of the gene related
to autosomal recessive juvenile parkinsonism. The entire gene
spans more than 500 kilobases. Mutations in this newly identified
gene appear to be responsible for the pathogenesis of the
disease, and the authors have named the protein product "Parkin".
The authors suggest the protein Parkin is apparently similar to
the ubiquitin family of proteins, which are involved in the
pathogenesis of several neurodegenerative diseases and are an
evident component of certain molecular entities in Alzheimer's
disease. Further investigation is necessary to establish the
exact physiological function of Parkin and how {parkin} gene
defects induce selective degeneration of specific neurons.
QY: Nobuyoshi Shimizu (shimizu@dmb.med.keio.ac.jp)
EMAIL
(Nature 9 Apr 98 392:605) (Science-Week 1 May 98)

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Related Background:

DISCOVERY OF GENE IMPLICATED IN PARKINSON'S DISEASE
Defects in the structure of the protein alpha-synuclein have been
implicated in several human brain pathologies, including
Alzheimer's disease and Creutzfeld-Jacob disease. Now a specific
type of familial, early-onset Parkinson's disease has been added
to the list. Mihael H. Polymeropoulos (20 authors at various
installations, US, IT, GR) have identified a mutation in the
alpha-synuclein gene in three unrelated families of Greek origin
exhibiting inherited early-onset Parkinsonism. A consensus is
growing that defects in the structure of alpha-synuclein may be
responsible for an array of human brain pathologies, with at
least some of the protein structural defects caused by inherited
genetic mutations. Alpha-synuclein has been previously shown to
be a presynaptic nerve terminal protein. The early visible
symptoms of Parkinsonism are produced by destruction of nerve
cells producing the hormone dopamine. In later stages of the
disease, destruction of other types of nerve cells occurs. This
new study does not provide evidence for a genetic basis for all
cases of Parkinsonism, but it serves as a pointer for researchers
studying the molecular biology of the disease.
(Science 27 Jun 97) (Science-Week 3 Jul 97)

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BOOK NOTES:

Sunny A. Auyang: FOUNDATIONS OF COMPLEX SYSTEMS THEORY
In Economics, Evolutionary Biology, and Statistical Physics
Cambridge Univ., 1998, 440p, US64.95
General features of complexity, theories of composite systems,
collective phenomena, emergent properties, stochastic processes.
Each topic is discussed with reference to statistical physics,
evolutionary biology, and economics.

M. Lynch and B. Walsh:
GENETICS AND ANALYSIS OF QUANTITATIVE TRAITS
W.H. Freeman, 1998, 803p, UK34.95
Theoretical and empirical applications of quantitative genetics,
reflecting the recent influx of quantitative-genetic thinking
into evolutionary biology. Includes latest techniques for QTL
analysis.

Abraham Pais et al: PAUL DIRAC
The Man and His Work
Cambridge Univ., 1998, 140p, US19.95
Lectures by Abraham Pais, Maurice Jacob, David Olive, Michael F.
Atiyah presented on the occasion of the dedication ceremony for a
plaque honoring Dirac in Westminster Abbey. The essays focus on
the relationship between Dirac's character and his scientific
achievements.

Max F. Perutz: I WISH I'D MADE YOU ANGRY EARLIER
Essays on Science, Scientists, and Humanity
Cold Spring Harbor Laboratory, 1998, 354p, US39
A collection of essays by the Nobel Laureate biochemist.
Detective stories, tales of conflict and battle, a woman's love
affair with crystals, a man's gruesome fascination with poison
gas, cancer cures as Nobel Laureates' geriatric illusions, social
relativists, and so on. A testament that science at all levels
of
endeavor is a passionate enterprise and the pursuit of natural
knowledge a sortie into the unknown.

John L. Phillips: THE BENDS
Compressed Air in the History of Science, Diving, and Engineering
Yale Univ., 1998, 272p, UK20
Explores the intertwining roles of science, technology,
engineering, medicine, and politics in the invention of
compressed air, the recognition and identification of
decompression sickness, and the 100-year-long process of learning
to understand and treat the bends. The author is a physician.

Orazio Svelto: PRINCIPLES OF LASERS
Fourth Edition
Plenum, 1998, 594p, US59.50
Standard topics in the field, plus physics of quantum confinement
semiconductor lasers, advanced laser resonators, femtosecond
lasers.

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