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ScienceWeek
SCIENCE-WEEK - Part 1/3
A Free Weekly Digest of the News of Science
February 13, 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."
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Contents of This Issue:
Part 1:
1. US Rejects Moratorium on Xenotransplantation Trials
2. Sheep Cloning Research Results: Questions and Answers
3. Comparative US University Chemistry PhDs.
4. On the New Gamma-Ray Astronomy
5. Laboratory Study of a One-Component Crystallized Ion Plasma
6. Detection of Intergalactic Red-Giant Branch Stars in a Cluster
7. Origin of Chondrules and the Formation of Jupiter
Part 2:
8. Discovery of Oldest Known Ant Fossils
9. A Molecular Analysis of Cellulose Biosynthesis
10. Sequence Analysis of an Arabidopsis Chromosome
11. A Model for Energy Transduction in ATP Synthase
12. An X-Ray Crystallography Study of T-Cell Antigen Receptors
13. Recognition of DNA Base Pairs by Synthetic Ligands
14. Yeast Engineered to Synthesize Steroids
15. Structure of a Phosphatidylinositol-Transfer Protein
16. Induction of Apoptosis by Injected Cytochrome C
Part 3:
17. Apoptosis: Release of Cytochrome C is Not Sufficient
18. Integrin-Mediated Short-Term Memory in Drosophila
19. A Gene Mutation Associated with Hereditary Human Hair Loss
20. Prevalence of Suicide After Natural Disasters
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1. US REJECTS MORATORIUM ON XENOTRANSPLANTATION TRIALS
Organ xenotransplantation is the transplantation of organs from
one species into another species, and in particular the
transplantation of animal organs into humans. In the context of
this report, "xenotransplantation" refers to animal-to-human
organ transplantation. As immunologists and molecular biologists
achieve increasing control over the biology of the transplant-
ation process, there has been a running debate about the relative
weights of the benefits and dangers of animal-to-human trans-
plantation. Despite mounting criticism from a number of
researchers, including vociferous opposition by the journal
Nature and its subsidiary Nature Medicine, US health officials
will apparently allow limited clinical trials of xenotransplant-
ation to proceed. At a meeting on 21 and 22 January (1998),
officials from the Food and Drug Administration, the Centers for
Disease Control and Prevention, and the National Institutes of
Health outlined plans involving stringent safeguards. There will
be rigorous standards to maintain disease-free donor animals, a
national registry of organ recipients, a tissue bank of samples
from donor animals and recipients, and a national policy advisory
committee. The guidelines are expected to be in final form by
this coming summer. QY: Gretchen Vogel
(Science 30 Jan 98)
-------------------
Related Background:
MORE CONTROVERSY CONCERNING POLICY ON XENOTRANSPLANTS
... In an editorial and several associated articles, the journal
Nature is now calling for an international moratorium on clinical
trials involving xenotransplantation, saying "a well-organized
and informed public debate should precede any action by
regulatory agencies." In a letter in the same issue of the
journal, Bach and Fineberg (Harvard University, US) also call for
a moratorium "on all forms of clinical xenotransplantation". QY:
Fritz H. Bach (Nature 22 Jan 98)
2. SHEEP CLONING RESEARCH RESULTS: QUESTIONS AND ANSWERS
In a rare public exposure of what is usually a private or at
least specialist-restricted dispute between researchers,
Sgaramella and Zinder (2 installations, IT US), in a letter to
the journal Science and in interviews with various news media,
have extensively criticized the Roslin (Scotland, UK) sheep
cloning group headed by Ian Wilmut. Sgaramella and Zinder focus
on the cloning of the sheep Dolly from an adult ovine cell, and
state there has been a lack of any confirmation of this experi-
ment, that the original experiment was poorly controlled, the
interpretations untested, corollary mitochondrial data not
provided, and so on. Sgaramella and Zinder suggest that endless
debates about cloning are less than correct in the face of both
"the scientific weaknesses of the experiment and the possible
impact on the societal credibility of science itself" by debates
based on "facts" only presumed. In a contiguous reply, Campbell
et al (including Ian Wilmut) provide details explaining the
protocols used in the original Dolly cloning, say the Dolly
cloning was an unexpected and unplanned tangent from other
research, say the fact that Dolly is a Finn Dorset ewe restricts
the origin of Dolly to a single laboratory culture existing at
the time, that corollary data have indeed been provided to third
parties, that only 11 months have passed since publication of the
results, and since the gestation period in sheep is 5 months,
there has not yet been enough time to complete similar experi-
ments and publish data. Despite this public conflict, the
apparent consensus among embryologists is that the work of the
Wilmut group will be confirmed. QY: Norton D. Zinder, Rockefeller
University, 1230 York Avenue, New York, NY 10021 US; Ian Wilmut,
Roslin Institute, Roslin, Midlothian E-125 9PS, Scotland, UK
(Science 30 Jan 98)
3. COMPARATIVE US UNIVERSITY CHEMISTRY PHDS.
The 1996 Annual Report of the American Chemical Society Committee
on Professional Training has been published. The number of PhDs
conferred in 1996 in chemistry has remained the same (at 2127),
while the number of PhDs conferred in chemical engineering has
risen from 584 to 690. The University of California Berkeley
produced the most PhD chemists (64), with the top 10 schools as
follows (numbers refer to chemistry PhDs conferred in 1996):
University of California Berkeley 64
Texas A & M College Station 46
Massachusetts Institute of Technology 43
Cornell University 38
University of Texas Austin 38
Purdue University 37
California Institute of Technology 36
University of Pennsylvania 36
Stanford University 36
University of California San Diego 30
QY: Diana Slade (Chem. & Eng. News 2 Feb 98)
4. ON THE NEW GAMMA-RAY ASTRONOMY
Gamma-rays are radiation of high energy, from about 10^(5)
electronvolts to more than 10^(14) electronvolts -- radiation
with the shortest wavelengths and highest frequencies -- the
gamma-ray region of the electromagnetic spectrum merging into the
adjacent lower energy x-ray region. Gamma-ray astronomy is the
study of gamma-rays from space, for the most part due to
nonthermal physics producing particle accelerations and other
far-from-equilibrium processes, and since gamma-rays cannot
penetrate the Earth's atmosphere, gamma-ray observations became
possible only when instruments were orbited in satellites. The
Compton Gamma-Ray Observatory (named after the physicist Arthur
Compton 1892-1962) was launched by space shuttle into a low-Earth
orbit in April 1991 with an expected mission duration of 6 to 10
years, and the 16-ton observatory contains 4 gamma-ray telescopes
on a stabilized platform. The Compton Observatory covers the
spectrum from 1.5 x 10^(4) electronvolts to 3 x 10^(10)
electronvolts. The Russian-French Granat mission, launched in
1989, has 2 gamma-ray instruments that image the sky from 3 x
10^(3) electronvolts to 1.3 x 10^(6) electronvolts. These two
observatories (with 6 instruments) have apparently provided
sensitivities and resolutions an order of magnitude greater than
anything previously obtained, with a covered photon energy
spectrum that comprises 6 orders of magnitude, a huge stretch of
electromagnetic radiation. ... ... Gehrels and Paul (2 install-
ations, US FR) review the recent history of gamma-ray astronomy,
the data collected by the newer detectors on the Compton Gamma-
Ray Observatory and the Granat mission, and the plans of gamma-
ray astronomers beyond Compton and Granat. So far, the data
produced by gamma-ray astronomy has impacted ideas concerning
sites of nucleosynthesis, black holes in our own galaxy, gamma-
ray bursts, and active nuclei of other galaxies. The authors
suggest that with the Compton and Granat observatories gamma-ray
astronomy made a great leap forward, and that missions in the
near future "promise that the next step will be just as great --
maybe even greater." QY: Jacques Paul, Saclay Nuclear Research
Center, Gif-sur-Yvette, FR.
(Physics Today February 1998)
5. LABORATORY STUDY OF A ONE-COMPONENT CRYSTALLIZED ION PLASMA
Bragg diffraction (also known as "Bragg scattering") is the
scattering of x-rays or neutrons by regularly spaced atoms in a
crystal, the interference occurring only at definite angles
(Bragg angles). The essential idea is that any set of equally
spaced planes in a crystal, provided each contains a sufficient
number of atoms as scatterers, can act as a set of mirrors for x-
rays -- with the exception that in this case the reflection
occurs only for discrete angles of incidence. In physics, a
plasma is usually taken as a neutral plasma, a completely or
nearly completely ionized gas consisting of an equal number of
positive and negative charges (e.g., positive ions and
electrons). In recent years, however, it has become possible,
albeit on a small scale, to use field methods to trap charges of
a single class. White dwarf stars are extremely dense and compact
stars that have undergone gravitational collapse, and neutron
stars are even more dense, with a body with a radius of 10 to 15
kilometers and a core so dense that its component protons and
electrons have merged into neutrons. ... ... Itano et al (6
authors at National Institutes of Standards and Technology
Boulder, US) now report the first observations, using optical
Bragg diffraction, of single crystals of a one-component plasma
containing 10^(5) to 10^(6) single-positive beryllium-9 ions at
particle densities of 10^(8) to 10^(9) per cm^(3). The authors
suggest knowledge of the properties of one-component plasma
crystals should be of importance for models of white dwarf stars
and neutron stars, both of which are believed to contain matter
in this form. QY: W.M. Itano
(Science 30 Jan 98)
6. DETECTION OF INTERGALACTIC RED-GIANT BRANCH STARS IN A CLUSTER
The Virgo cluster is a giant irregular cluster of galaxies, the
nearest large cluster, and it consists of several thousand
galaxies, most of which are spirals. Galactic clusters are of
intense interest in cosmology, particularly the mechanisms of
their evolution. Intergalactic stars are stars in a galactic
cluster that by one gravitational process or another have been
essentially dissociated from any particular galaxy to become
independent in the space between the galaxies, and the existence
of such stars has been suspected for many years from measurements
of diffuse light in blank regions and detection of planetary
nebulae (clouds of gas ejected from dying stars). Red giants are
giant stars with a surface temperature 2000 to 4000 degrees
kelvin and a diameter 10 to 1000 times greater than the Sun, and
they are one of the final phases in the evolution of a normal
star. A red-giant "branch" star is a red-giant star that has
evolved along a normal branch off the stellar temperature-
luminosity curve known as the Hertzsprung-Russell diagram.
... ... Ferguson et al ( 3 authors at 3 installations, US UK) now
report the direct detection of 630 intergalactic stars, appar-
ently red-giant branch stars, in a blank field in the Virgo
cluster. The authors suggest their data indicate these stars form
approximately one-tenth of the total stellar mass of the
cluster.
QY: Henry C. Ferguson (Nature 29 Jan 98)
7. ORIGIN OF CHONDRULES AND THE FORMATION OF JUPITER
Chondrites are a type of stony meteorite consisting of an
agglomeration of millimeter-sized globules (chondrules) that are
thought to be unchanged since the original condensation out of
the gaseous nebula from which the sun and solar system formed.
Planetesimals are bodies with dimensions of 10^(-3) to 10^(3)
meters that are believed to form planets by a process of
accretion. The term "accretion" refers to an aggregation, an
increase in the mass of a body by the addition of smaller bodies
that collide and adhere to it, provided the relative velocities
are low enough for coalescence. In principle, one can distinguish
"first generation" planetesimals from second (or third, etc.)
generation planetesimals formed by the breakup of first generat-
ion planetesimals, all of the events determined by granule
densities, planetesimal densities, gravitational fields, orbits,
orbital velocities, and so on. In addition, in complex gravitat-
ional systems consisting of many small orbiting bodies influenced
by the gravitational field of a large orbiting body, there are
"resonances" that may arise, amplifications of gravitational
perturbations due to various periodicity parameters, and these
perturbations may play an important role in the gravitational
evolution of the entire system. The term "bow shock" refers to
the shock wave produced by the interaction of the supersonic
solar wind (the continuous flow of hydrogen and helium gas from
the sun) with the magnetic field of a planet (in this case,
Jupiter). The chondrules are considered an important theoretical
link to the origin and early development of our solar system, and
various models have been formulated based on their chemistry and
physical properties. ... ... Now Weidenschilling et al (3 authors
at 3 installations, US IT) present a model for the production of
chondrules by heating of debris from disrupted first-generation
planetesimals, with Jovian resonances exciting planetesimal
orbiting eccentricities enough to cause collisional disruption
and melting of dust by bow shocks in the nebular gas. The authors
suggest the age of chondrules may indicate the times of Jupiter's
formation and dissipation of gas from the asteroidal region, and
that their model reconciles the present apparently incompatible
temporal and dynamical constraints on theory produced by
observations and analysis. QY: S.J. Weidenschilling
(Science 30 Jan 98)
(continued in Part 2)
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
SCIENCE-WEEK - Part 2/3
A Free Weekly Digest of the News of Science
February 13, 1998
Contents of Part 2:
8. Discovery of Oldest Known Ant Fossils
9. A Molecular Analysis of Cellulose Biosynthesis
10. Sequence Analysis of an Arabidopsis Chromosome
11. A Model for Energy Transduction in ATP Synthase
12. An X-Ray Crystallography Study of T-Cell Antigen Receptors
13. Recognition of DNA Base Pairs by Synthetic Ligands
14. Yeast Engineered to Synthesize Steroids
15. Structure of a Phosphatidylinositol-Transfer Protein
16. Induction of Apoptosis by Injected Cytochrome C
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8. DISCOVERY OF OLDEST KNOWN ANT FOSSILS
The ants are one of the most successful extant species, until now
believed to have first appeared about 40 million years ago. With
the wasps, bees, and termites, they are remarkable as invertebr-
ates exhibiting colonies that involve division of labor and a
complex social organization. The so-called "Turonian" geologic
stage (92 million years ago) corresponds approximately to the
Upper or Middle Cretaceous period. ... ... Agosti et al (3
authors at American Museum of Natural History New York, US) now
report fossil ants, including a new genus of Ponerinae,
approximately 50 million years older than the previous oldest
specimens. The discoveries were made in New Jersey (US) in amber
from the Turonian stage, and include 3 worker and 4 male ants.
The authors suggest the specimens have important implications for
dating the origin of ants, and extend the age of an extant ant
subfamily back about 50 million years.
QY: Donat Agosti (Nature 29 Jan 98)
9. A MOLECULAR ANALYSIS OF CELLULOSE BIOSYNTHESIS
Cellulose, a crystalline beta-1,4-glucan, is the most abundant
polymer on Earth, with a central involvement in plant
morphogenesis and of great industrial importance. The cellulose
synthases are the enzymes that catalyze the polymerization of
cellulose in plants, but until now the genes that code for these
enzymes have not yet been identified. Arabidopsis (thale cress)
is a weed of the mustard family with a small genome (120 million
base pairs), the plant popular as a research tool because it is
easily maintained and easy to manipulate genetically.
... ... Arioli et al (14 authors at 5 installations, AU DE FR)
now report that a combination of chemical, ultrastructural, and
gene cloning methods reveal that the Arabidopsis plant gene locus
is the locus that encodes the catalytic subunit of
cellulose synthase. The authors suggest the gene product can be
used to manipulate the production and physical properties of
cellulose, and that studies of mutations of the gene may provide
a link between cellulose production and plant morphogenesis.
QY: Richard E. Williamson
(Science 30 Jan 98)
10. SEQUENCE ANALYSIS OF AN ARABIDOPSIS CHROMOSOME
The Arabidopsis plant (cf. previous report) is an important
laboratory species, and it is presently the model for
physiological, biochemical, cell biological, and developmental
studies of over 250,000 plant species. ... ... Bevan et al (67
authors at 21 installations, UK US NL DE BE FR IE ES GR) report a
1.9-megabase contiguous DNA sequence of chromosome 4 of
Arabidopsis thaliana, and that analysis of the sequence reveals
an average gene density of one gene every 4.8 kilobases, with 54%
of the predicted genes having significant similarities to known
genes. The authors also found the sequence of a disease-
resistance gene locus and the sequence of several classes of
genes not previously encountered in plants. The identified
sequence is only 1.5% of the Arabidopsis genome, but it is the
largest contiguous segment of plant DNA sequenced to date and
provides much detailed information. The authors suggest it is now
clear that a straight-forward shotgun sequencing strategy can
generate contiguous sequences from nearly all of the low-copy
regions of the Arabidopsis genome.
QY: M. Bevan (Nature 29 Jan 98)
11. A MODEL FOR ENERGY TRANSDUCTION IN ATP SYNTHASE
ATP (adenosine triphosphate) is the most important chemical
energy source in all living cells, intimately involved in various
cell functions and cell metabolism, and an entity in numerous
cyclic chemical pathways involved in the synthesis of components.
In mitochondria (eukaryotic cellular organelle type involved in
energy production), bacteria, and chloroplasts (plant cell
organelle type involved in photosynthesis) the free energy stored
in transmembrane ion gradients is used to catalyze the synthesis
of ATP by the membrane-bound enzyme ATP synthase. This enzyme
apparently consists of a proton channel associated with three
catalytic sites that cooperate in the synthesis of ATP, and it
has been suggested that during the process of synthesis coupled
to proton transfer there are important macroscopic mechanical
displacements of the complex, the complex acting as a rotating
cam as it produces 3 ATPs per 12 protons passing through the
"motor". ... ... Elston et al (3 authors at University of
California Berkeley, US) now present a model for a mechanism for
transducing free energy stored in an ion gradient into a rotary
torque, the analysis delineating quantitative conditions that can
generate the power required for ATP synthesis. The authors
suggest that in addition to elucidating the mechanisms for torque
generation, the model provides a framework for integrating the
kinetic, thermodynamic, and mechanical aspects of proton-motive
energy transduction in living cells.
QY: George Oster (Nature 29 Jan 98)
12. AN X-RAY CRYSTALLOGRAPHY STUDY OF T-CELL ANTIGEN RECEPTORS
An antibody is a protein molecule produced by the immune system
of vertebrate organisms, the molecule designed to specifically
interact with a particular invading foreign chemical entity
called "an antigen". Antibodies are produced and released by so-
called "B-cells" of the immune system, and antibody production is
part of the response of the immune system response to invasion by
foreign biological material. Another part of the immune system
response is the activation of various types of T-cells, whose
genomes are modified by interaction with foreign entities so that
T-cells can produce receptors that will then specifically recogn-
ize these entities. In general, the interaction of specific
antigens with specific cell receptors is the basis for the oper-
ation of the immune system, and there is much research effort
concerned with unraveling the details of the molecular inter-
actions. The T-cell receptors are apparently cell surface
glycoproteins involving 4 types of polypeptide chains: alpha,
beta, gamma, and delta, with variable (V) or constant (C) reg-
ions, and the T-cells receptors are either the alpha-beta variety
or the gamma-delta variety, with associated differences in
antigen recognition mechanisms. ... ... Li et al (6 authors at 3
installations, US AU) report the crystal structure of the
V(variable)-delta domain of a human gamma-delta T-cell antigen
receptor at 1.9 angstroms resolution. The authors suggest their
results provide the first direct evidence that gamma-delta T-cell
antigen receptors are structurally distinct from alpha-beta T-
cell antigen receptors, and that recognition of certain antigens
by gamma-delta T-cell antigen receptors may resemble antigen
recognition by antibodies.
QY: Roy A. Mariuzza
(Nature 29 Jan 98)
13. RECOGNITION OF DNA BASE PAIRS BY SYNTHETIC LIGANDS
Amides are organic compounds derived from ammonia by substitution
of one or more of its hydrogen atoms by organic acid groups, and
polyamides are synthetic polymers in which the monomers are
linked by the group -NH-CO-. Nylon is a polyamide.
... ... White et al (5 authors at California Institute of
Technology, US) report the synthesis of small polyamide molecules
that can recognize any predetermined sequence of DNA and bind to
the sequence with affinities and specificities similar to those
of DNA-binding proteins. The authors suggest this approach offers
a potential technique for the synthetic regulation of gene
expression. QY: Peter B. Dervan
(Nature 29 Jan 98)
14. YEAST ENGINEERED TO SYNTHESIZE STEROIDS
The natural steroids are substances that arise from the oxidative
cyclization of squalene, and many of them are important hormones
(i.e., chemical messengers). Progesterone is a female steroid
hormone involved in the maintenance of pregnancy and the suppr-
ession of ovulation, and pregnenolone is a chemical intermediate
in the biological synthesis of progesterone. ... ... Pompon et al
(CNRS Gif-sur-Yvette, FR) report the genetic engineering of yeast
(Saccharomyces cerevisiae) to synthesize pregnenolone and to
convert it to progesterone, the procedure involving the deletion
of one gene and insertion of 5 others. The authors suggest this
new approach can simplify industrial production of steroid
hormones. QY: Denis Pompon, CNRS, Gif-sur-Yvette, FR. (Nature
Biotechnology 16:186 1998) (Chem. & Eng. News 2 Feb 98)
15. STRUCTURE OF A PHOSPHATIDYLINOSITOL-TRANSFER PROTEIN
The biological phospholipids, which are essentially long-chain
fatty acids with a phosphate polar group at one end, are among
the most important chemical substances in biological systems,
responsible in various ways for the individualization of cells
and the compartmentalization of the interior of cells as a result
of the ability of phospholipids to form self-organizing layers in
surfaces, spheres, cylinders, and so on. Phosphatidylinositol-
transfer protein is an enzyme that catalyzes the exchange of the
phospholipids phosphatidylinositol and phosphatidylcholine
between membrane bilayers, and various forms of this enzyme are
apparently present in systems ranging from yeasts to humans....
... Sha et al (4 authors at University of Alabama, US) report a
three-dimensional structure for the yeast phosphatidylinositol-
transfer protein at 2.5 angstroms resolution, the protein
consisting of 2 distinct domains, one of which forms a hydro-
phobic pocket and represents the phospholipid binding domain.
They have also identified an unusual surface helix that may drive
the phospholipid exchange mediated by this protein. The authors
suggest their data provide the first structural insights into the
function of a phosphatidylinositol-transfer protein and new
information concerning the architecture of an entire family of
evolutionarily conserved proteins.
QY: Vytas A. Bankaitis
(Nature 29 Jan 98)
16. INDUCTION OF APOPTOSIS BY INJECTED CYTOCHROME C
The cytochromes, categorized as hemoproteins with differing
porphyrin groups, are widely distributed respiratory (oxygen-
utilizing) catalysts involved in the electron transport chain of
living cells. They do not combine with substrates, but alternate
between Fe(2+) and Fe(3+) states. There are various cytochromes,
with cytochrome c present in the greatest amounts, and most
importantly in the mitochondria of eukaryotic cells. Apoptosis is
programmed cell death produced by control mechanisms designed to
destroy defective cells or cells whose destruction is necessary
for the specialization of tissues. Adrenocortical tumor cells are
tumor cells arising from the cortex of the adrenal gland(s);
epithelial cells are cells lining the interior of body cavities
or exposed surfaces of the body; fibroblasts are a type of
connective tissue cell secreting structural proteins (e.g.,
collagen); and promyelocytic leukemia cells are large uninuclear
cells circulating in the blood of persons with leukemia of a type
of blood cell called myelocytes (bone marrow granulocytes).
Caspase is a type of protease, an enzyme that degrades protein by
hydrolysis, and it has been implicated in apoptosis. Apparently,
when cells are exposed to stimuli that trigger apoptosis,
cytochrome c is rapidly released from mitochondria into the
cytoplasm, and there cytochrome c activates caspases that begin
the destruction of the cell. ... ... Zhivotovsky et al (4 authors
at 2 installations, SE NO) report that microinjection into cells
of cytochrome c activates apoptosis, the effect seen in various
cell types, including adrenocortical tumor cells, normal rat
kidney epithelial cells, mouse embryonic fibroblasts, and rat
promyelocytic leukemia cells, and that the effect is caspase-
dependent. QY: Stenn Orrenius
(Nature 29 Jan 98)
-------------------
Related Background:
PROTEASES AS MEDIATORS OF APOPTOSIS
Proteases are a class of enzymes that hydrolyze proteins,
splitting them into various groups of subunits, with the sites of
hydrolysis dependent on the particular enzyme and the protein
substrate. Actin is a structural protein present in all cells
as a constituent of the cell cytoskeleton, and gelsolin is a
protein that breaks actin filaments and causes a gel-sol
conversion -- a conversion of a gelatin-like system to a solution
(liquid) system. This type of conversion is ordinary in certain
cell types under certain conditions, but it is also seen in
apoptosis (programmed cell death) when the cytoskeleton is
destroyed and the cytoplasm liquified. Srinivas Kothakota et al
(11 authors at 3 installations, US) report that the protein
gelsolin is the primary substrate for the caspase-3 protease
family that has been implicated in apoptosis. Gelsolin cleavage
products cause multiple cell types to round up, detach from the
cell culture plate, and undergo nuclear fragmentation. Cells
isolated from genetically engineered mice lacking gelsolin showed
marked delays in apoptosis onset following apoptosis induction,
while wild-type cells did not show these delays. The authors
suggest that cleaved gelsolin may be one of the physiological
effectors that produce morphological changes during apoptosis.
QY: David J. Kwiatkowski
(Science 10 Oct 97)
-------------------
NEW EVIDENCE OF LIPID INVOLVEMENT IN BRAIN CELL DEATH
Apoptosis (programmed cell death) is a rapid and specific process
involving the production of a number of enzymes in the cell that
is to be destroyed. This programmed destruction is not always
harmful, or a result of cellular damage of one sort or another.
In humans, for example, the lack of webbing between fingers and
toes is a result of apoptosis of cells of webbing tissue occur-
ring during embryological development, the apoptosis in this case
being a normal part of the larger embryological program. In the
mature organism, apoptosis is the usual method of removing
damaged cells after these cells are recognized to be damaged by
one mechanism or another. It is known that normal cells carry an
apoptosis receptor on their surfaces, called CD95, and that when
this surface receptor is cross-linked by its specific ligand,
this triggers the sequence of events known as apoptosis. In the
apoptosis sequence, certain proteolytic enzymes inside the cell
are activated, and in addition a variety of lipids that cause
cell dysfunction are synthesized. Gangliosides, a type of lipid
with covalently linked sugars, is one such lipid, and it is
evident in certain pathological processes, particularly Niemann-
Pick disease, a lipid-storage disease one of whose symptoms is
mental retardation. Now there is a report by Ruggero De Maria et
al (University of Rome, IT) that indicates a transient accumulat-
ion of gangliosides occurs when the CD95 apoptosis receptor is
triggered. The gangliosides are evidently active participants in
the apoptosis process, since exposure of cells to gangliosides,
which easily penetrate the cell membrane, itself induces
apoptosis. QY: R. Testi (Science 12 Sep)
(continued in Part 3)
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
SCIENCE-WEEK - Part 3/3
A Free Weekly Digest of the News of Science
February 13, 1998
Contents of Part 3:
17. Apoptosis: Release of Cytochrome C is Not Sufficient
18. Integrin-Mediated Short-Term Memory in Drosophila
19. A Gene Mutation Associated with Hereditary Human Hair Loss
20. Prevalence of Suicide After Natural Disasters
----------------------------------------------------------------
17. APOPTOSIS: RELEASE OF CYTOCHROME C IS NOT SUFFICIENT
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. Bcl-2
is a protein that interferes with the activation of caspases by
preventing the release of cytochrome c, and Bax is a homolog of
Bcl-2 that promotes apoptosis. The term "membrane blebbing"
refers to the macroscopic blistering of the surfaces of cells
when they die under certain conditions. ... ... Rosse et al (8
authors at 2 installations, CH AT) report that in cells
transiently transfected with the gene , the protein Bax
localizes to mitochondria and induces the release of cytochrome
c, activation of caspase-3, membrane blebbing, nuclear fragment-
ation, and cell death. It was also found that cells overexpress-
ing both proteins Bcl-2 and Bax show no signs of caspase activ-
ation and survive with significant amounts of cytochrome c in the
cytoplasm. The authors suggest their findings indicate Bcl-2 can
interfere with Bax-induced apoptosis downstream and independent
of cytochrome c release.
QY: Christoph Borner
(Nature 29 Jan 98)
18. INTEGRIN-MEDIATED SHORT-TERM MEMORY IN DROSOPHILA
Complementing more than a century of research by psychologists on
human memory, recent animal behavioral and cellular studies have
also revealed two broad categories (or phases) of memory: short-
term memory and long-term memory. Short-term memory, lasting from
minutes to hours, is believed to involve rapid and transient
biochemical changes in nerve cells that affect the dynamics of
synapses, while long-term memory, which lasts from days to years,
is believed to involve restructuring of synapses as a result of
altered gene expression. In general, sensory conditioning
involves an effective neural coupling between a previously
neutral sensory stimulus (S1) and a particular organismic
response (R) when that stimulus is temporally coupled (preceding)
another stimulus (S2) that is not neutral and for which the
organism is hard-wired to produce the same response (R). The
classical paradigm is the Pavlovian dog salivating (R) in
response to a bell (S1) after the sound of the bell has been
associated with the presentation of food (S2). In the context of
this report concerning the fruit fly Drosophila, the term
"olfactory conditioning" refers to an avoidance conditioning
procedure involving the pairing of the presentation of an odor
with aversive electroshock, and the quantitative analysis of
behavioral results used to assess learning and memory perform-
ance. The term "plasticity" as used in this report refers to the
alteration of the behavior of nerve cells and of the organism as
a whole, in particular as an apparent result of experience.
Alpha-integrin is a type of cell surface receptor known to
mediate cell adhesion and chemical messenger signal
transduction.... ... Grotewiel et al (5 authors at Baylor College
of Medicine, US) report the isolation of a new Drosophila memory
gene, volado (called vol), which encodes a new alpha-
integrin, and that vol mutations have a dominant effect on
short-term memory following olfactory conditioning. Conditional
expression of vol just before training rescues the memory
deficit of vol mutants. The rescue is reversible, supporting a
dynamic role for integrins in neuronal and behavioral plasticity.
The authors suggest that integrin-mediated signaling or synaptic
restructuring underlie the formation, stability, or retrieval of
short-term memory. QY: Ronald L. Davis
(Nature 29 Jan 98)
-------------------
Related Background:
INTEGRIN CHANGES AND REGULATION OF NEURON ADHESION
The integrins are a family of glycoprotein cell membrane recept-
ors that bind to extracellular matrix components at the outer
membrane surface, and interact with cytoskeletal components at
the inner membrane surface. Integrins are thus important in cell-
extracellular matrix interactions and in cell-cell adhesion,
which makes them a central component in the formation and struct-
ure of various tissues. Cell adhesion is simply the ability of
cells to remain in association with each other. Sensory neurons
are nerve cells specifically designed to act as energy trans-
ducers, or to receive input from energy transducers, and to
produce an output that is propagated to other nerve cells. Nerve
cells in tissue culture (and nerve cells in a developing nervous
system and nerve cells undergoing regeneration) exhibit growth of
axons and dendrites, and this growth is called "neurite out-
growth". M. L. Condic and P. C. Letourneau (University of Utah,
US; University of Minnesota, US) report that the concentration of
integrin ligand regulates the amount of integrin receptor
expressed on the surface of sensory neurons, with the relation-
ship being inverse -- when ligand concentration is low, integrin
receptor amount increases -- and that ligand concentration
determines surface concentrations of integrin by changing the
rate at which the receptor is removed from the cell surface. In
addition, increased expression of integrin at the cell surface is
related to increased neuronal cell adhesion and neurite out-
growth. The authors suggest that integrin regulation is the key
process in the development and regeneration of nerve cell axons.
QY: M. Condic (Nature 23 Oct 97)
19. A GENE MUTATION ASSOCIATED WITH HEREDITARY HUMAN HAIR LOSS
Alopecia is a general term for a disease characterized by loss of
hair, and alopecia universalis is a specific disease character-
ized by loss of hair from all parts of the body. A kindred is an
aggregate of genetically related persons, and a recessive trait
is a trait due to a particular allele (one of two or more
different genes occupying the same locus on a chromosome) that
does not manifest itself in the presence of other alleles that
generate traits dominant to it. Recessive traits are caused by
the inheritance of a relevant allele from each parent. The term
"murine" is generic for the mouse (Muridae). A missense mutation
is a mutation that produces in the expressed protein the substit-
ution of one amino acid for another. A "zinc finger" is a zinc-
binding domain in a protein structure, relatively common in gene
regulatory proteins, and a transcription factor protein is a
protein involved in the transcription of DNA code into RNA code.
... ... Ahmad et al (17 authors at 5 installations, US PK UK)
report the study of a kindred with a rare recessively inherited
type of alopecia universalis from which the human homolog of a
murine gene hairless was localized to chromosome 8p12, and that
a missense mutation was found in affected individuals. The
authors suggest the human hairless gene apparently encodes a
single zinc finger transcription factor protein with restricted
expression in the brain and skin.
QY: Angela M. Christiano (Science 30 Jan 98)
20. PREVALENCE OF SUICIDE AFTER NATURAL DISASTERS
Krug et al (7 authors at Centers for Disease Control and
Prevention, US) report an analysis of federally declared
disasters between 1982 and 1989, comparing suicide rates before
and after those disasters in the affected counties and in the
entire US. Suicide rates increased in the 4 years after floods by
13.8%, in the 2 years after hurricanes by 31%, in the first year
after earthquakes by 62.9%. Rates computed in a similar manner
for the entire US were stable. The increase in suicide rates was
found for both sexes and for all age groups. The suicide rates
did not change significantly after tornadoes or severe storms.
The authors suggest these results confirm the need for mental
health support after severe disasters. QY: Etienne G. Krug,
Centers for Disease Control and Prevention, Atlanta, GA 30333 US
(New England J. Med. 5 Feb 98)
---------------------------------------------
BOOK NOTES
American Chemical Society:
CHEMICAL SCIENCES GRADUATE SCHOOL FINDER 1997-1998
American Chemical Society, 1997, 800p, US21.95
Information on graduate programs in a range of disciplines within
the chemical sciences. 235 entries for departments in 162
institutions in US and CA, courses leading to Master's or PhD in
chemistry or allied fields. Student population, admission and
degree requirements, costs and financial aid, faculty members and
their research specialties, research facilities and equipment.
Application instructions, fields of study and geographic indexes,
etc. A useful reference at a reasonable price.
J.H. Duffus (ed.): CARCINOGENICITY OF INORGANIC SUBSTANCES
Risks from Occupational Exposure
American Chemical Society, 1997, 296p, US155
Attempts to "define the state of scientific knowledge about
carcinogenicity of metals, their compounds, and inorganic
substances generally." Intended for chemists involved in risk
assessment, health and safety, and toxicology.
J.H. Duffus (ed.): SUBSTANCES OF ABUSE
An Assessment of Carcinogenicity
American Chemical Society, 1997, 134p, US113
Discusses the long-term adverse effects, particularly
carcinogenetic effects, of substances of abuse such as
therapeutic industrial chemicals and "crack" cocaine. Discussion
in 3 parts: Drugs, Anesthetics, Industrial Solvents. Intended for
occupational health workers, toxicologists, drug metabolism
professionals. An expensive little volume.
R.A. Gross et al (eds.): ENZYMES IN POLYMER SYNTHESIS
American Chemical Society, 1997, 230p, US99.95
An introduction to the use of enzymes in polymer science.
Explores enzyme-based synthesis and discusses modification of
polymers by enzymes. For polymer and materials chemists and
chemical engineers.
G. Jerkiewicz et al (eds.):
SOLID-LIQUID ELECTROCHEMICAL INTERFACES
American Chemical Society, 1997, 368p, US110.95
Applications of low-energy electron diffraction, Auger electron
spectroscopy, and x-ray photoelectron spectroscopy to the study
of the solid-liquid interface. Also discusses scanning tunneling
microscopy and atomic force microscopy as applied to studies of
structures of substrates and adsorbates during electrochemical
measurements. Includes a theoretical approach to modeling of the
electrochemical interface.
N. Leontis and J. SantaLucia Jr. (eds.):
MOLECULAR MODELING OF NUCLEIC ACIDS
American Chemical Society, 1997, 450p, US129.95
Discusses the role of NMR, x-ray crystallography, and other
spectroscopic methods in the molecular modeling of DNA and RNA.
Molecular dynamics simulations using particle mesh methods, RNA
secondary structure prediction using dynamic and genetic
algorithms, thermodynamics of nucleic acid folding, 3D structure
prediction based on sequence information. For biochemists,
medicinal chemists, and pharmaceutical chemists.
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