ScienceWeek

SCIENCE-WEEK

A Weekly Email Digest of the News of Science

A journal devoted to the improvement of communication
between the scientific disciplines, and between scientists,
science educators, and science policy makers.

February 12, 1999 -- Vol. 3 Number 7

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

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Contents of This Issue:

1. A Call for an Independent Drug Safety Board
2. Inflation in a Low-Density Universe
3. The Dusty Atmosphere of a Brown Dwarf Star
4. On Heat Shock Proteins
5. A Hydrogenosome with a Genome
6. On Models of Immune Memory

Complete List of SW Focus Reports

Notices, subscription information, editorial contacts, etc.

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1. A CALL FOR AN INDEPENDENT DRUG SAFETY BOARD
New technologies in molecular biology and synthetic organic
chemistry are already having a considerable impact on the design
and manufacture of new pharmaceutical agents for clinical and lay
consumer use. We are apparently only at the beginning of a new
era in pharmaceutical drug design, and one question of central
importance is whether existing procedures to ensure the safety of
new drugs made available to physicians and lay consumers are
adequate. ... ... A.J.J. Wood et al (3 authors 2 installations,
US) are now proposing the establishment of an independent drug
safety board in the US, the authors making the following points:
1) Adverse reactions to drugs are an important cause of morbidity
and mortality, and it has been recently estimated that
approximately 100,000 Americans die each year as a result of such
adverse reactions -- which makes adverse drug reactions one of
the most common causes of death. 2) Independent agencies exist to
investigate airline accidents, railroad mishaps, and radiation
spills, and to make recommendations for their prevention.
However, no independent entity exists with the responsibility to
monitor and investigate adverse events due to drugs (and medical
devices) and to make recommendations to prevent them. 3) At
present, after a drug is approved for marketing, the community
relies on a voluntary reporting system based on the assumption
that a drug is safe unless case reports of adverse effects call
that assumption into question. Such a process led to the
withdrawal of dexfenfluramine after the publication of a report
describing valvular heart lesions in 24 patients. The authors
state: "It is remarkable that at a time when the technology for
collecting and analyzing large amounts of data is readily
available, an independent, comprehensive, and systematic program
of post-marketing drug surveillance does not exist." 4) The
authors propose that a post-marketing drug-safety program which
is independent of the agency responsible for drug approval in the
US (the US Food and Drug Administration) needs to be established.
5) The authors conclude: "We must expect that predicted and
unpredicted adverse events from drugs will continue to occur. If
we accept that the true safety profile of a new drug is dependent
on the "experiment" that necessarily follows the drug's release
into the marketplace, then we must fund and implement mechanisms
to ensure that the experiment is properly monitored, the data
appropriately analyzed, and the conclusions disseminated
rapidly."
-----------
A.J.J. Wood et al: Making medicines safer -- The need for an
independent drug safety board.
(New England J. Med. 17 Dec 98 339:1851)
QY: Alastair J.J. Wood, Vanderbilt University 615-322-7311
-------------------
Summary by SCIENCE-WEEK [http://scienceweek.com] 12Feb99


2. INFLATION IN A LOW-DENSITY UNIVERSE
There is an apparent consensus among cosmologists that recent
observational evidence is not consistent with the current
"*inflation theory" of the early evolution of the Universe, and
that to keep this theory relevant requires either the postulate
of an exotic form of energy or the addition of "a layer of
complexity" to inflation theory. ... ... M.A. Bucher and D.N.
Spergel (2 installations, UK US) present a review of the second
option, the authors making the following points: 1) Despite its
success, the standard *Big Bang theory cannot answer several
important questions: Why is the density and temperature of the
present Universe so uniform? Why did the early Universe have any
density variations at all? Why is the rate of cosmic expansion
just enough to counteract the collective gravity of all the
matter in the Universe? 2) The failure of the standard Big Bang
theory to answer these questions provoked, in the 1980s, the
formulation of the theory of inflation by Guth, Sato, Linde,
Albrecht, Steinhardt and others. 3) Inflation theory predicts a
flat (i.e., Euclidean) and uniform Universe, with an observed
value of the *Omega parameter either exactly 1 or so close to 1
that the deviation is not detectable. The implication of an Omega
value of 1 is that the cosmic gravitational energy exactly equals
the cosmic kinetic energy (i.e., the energy contained in the
motion of matter as space expands). The problem is that a wide
variety of recent astronomical observations involving galaxy
clusters and distant supernovae suggest that gravity is too weak
to combat cosmic expansion, that the density of matter must be
much less than predicted, and that the value of the Omega
parameter is equal to approximately 0.3. 3) The authors propose
there are 3 ways to interpret this result: a) Standard inflation
theory is completely wrong. Or b) Standard inflation theory is
correct: the Universe is flat, but an additional new form of
energy exists, and this is responsible for what appears to be an
accelerating expansion. Or c) Standard inflation theory is
partially correct, and its assumption of the inevitability of a
flat Universe needs to be revised. 4) The focus of the authors is
on the 3rd option. They review a revision of standard inflation
theory, the revision involving the introduction of a "*false-
vacuum decay" preceding the standard inflation, this false-vacuum
decay producing nonuniform "bubbles" of expansion [*Note #1]. The
new conception is called "open inflationary theory". 5) The
authors state that at the current levels of precision,
observations cannot distinguish between the predictions of the 2
theories of inflation. The authors suggest the "moment of truth"
will come with the planned deployment late next year of the
*Microwave Anisotropy Probe, and the launch in 2007 of its
European counterpart, *Planck. These satellites will perform
observations similar to those of the *Cosmic Microwave Background
Explorer (COBE) nearly a decade ago, but at a much higher
resolution. The authors suggest these new satellites will be able
to resolve which of the 3 theoretical options is correct: a) an
abandonment of any inflation theory; b) standard inflation theory
with a new form of energy; c) open inflation theory.
-----------
M.A. Bucher and D.N. Spergel: Inflation in a low-density
Universe.
(Scientific American January 1998)
QY: Martin A. Bucher, University of Cambridge, UK.
-----------
Editor's note: In addition to the background material below,
further material on this subject was presented last week in the
SW issue of 5 Feb 99. Also, there are a number of relevant SW
Focus Reports available at [http://scienceweek.com/swfr.htm].
-----------
Text Notes:
... ... *inflation theory: The inflationary model, first proposed
by Alan Guth in 1980, proposes that quantum fluctuations in the
time period 10^(-35) to 10^(-32) were quickly amplified into
large density variations during the "inflationary" 10^(50)
expansion of the universe in that time frame.
... ... *Big Bang theory: The Big Bang theory is the general
cosmological model that proposes that all matter and radiation in
the universe originated in an explosion at a finite time in the
past.
... ... *Omega parameter: Another approach to the Omega parameter
is to define it as the ratio of the density of matter (or energy)
in the Universe to the theoretical density required for flatness.
An Omega with a value of greater than 1 implies a closed
Universe; a value less than 1 implies an open Universe; a value
equal to 1 implies a flat Universe.
... ... *false-vacuum decay: A "false vacuum" is a peculiar state
of matter which has never been observed but whose properties are
unambiguously predicted by *quantum field theory. Essentially,
the idea of a false vacuum refers to a miniature energy minimum
above the true minimum, a saddle "trap". The most peculiar
property of the false vacuum is probably its pressure, which is
both large and negative. The term "false-vacuum decay" refers to
a breaking out of the trap, in this case via *quantum mechanical
tunneling through the miniature energy barrier, and then a fall
to the true zero-point (minimum vacuum energy). The application
of the idea of false vacuum to the inflation model was already
well underway in the late 1980s by Guth and others.
... ... *quantum field theory: Quantum field theory is the
mathematical fusion of quantum mechanics with special relativity
theory.
... ... *quantum mechanical tunneling: "Tunneling" is a quantum
mechanical phenomenon involving an effective penetration of an
energy barrier resulting from the width of the barrier being less
than the wavelength of the particle.
... ... *Note #1: It should be noted that this idea was already
described in the late 1980s by Alan Guth and others.
... ... *Microwave Anisotropy Probe: Information on this
satellite project can be found at URL [http://map.gsfc.nasa.gov].
... ... *Planck: Information on this satellite project can be
found at [http://astro.esctec.esa.nl/SA-general/Projects/Planck].
... ... *Cosmic Microwave Background Explorer (COBE): A NASA
orbiting satellite launched in 1989 and dedicated to the study of
the *cosmic microwave background radiation. The most important
results were the discoveries of irregularities in the cosmic
background radiation on the level of one part in 10^(5), and the
confirmation that the spectrum of the cosmic background radiation
is that of a black body with a temperature of 2.73 degrees
kelvin.
... ... *cosmic microwave background radiation: The cosmic
microwave background is black-body radiation (the emission
radiation of a perfect absorber of radiation) at a present
temperature of 2.73 degrees Kelvin, and has an almost equal
intensity in all directions in space. The deviations from
isotropic intensity, however, are of extreme importance in
theoretical cosmology. The cosmic background radiation is
predicted by the Big Bang theory and is considered one of the
most important pieces of evidence for it.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 12Feb99
-------------------
Related Background:
ASTROPHYSICS: ON ACCELERATING COSMIC EXPANSION
The idea of cosmic expansion derives from the observation that
radiation from distant galaxies is *redshifted, and the consensus
is that the distance between clusters of galaxies is continuously
increasing, with all galaxies beyond the Local Group apparently
receding from us [*Note #1]. In other words, the Universe as a
whole is expanding, a phenomenon discovered by Edwin Hubble in
1929 but previously suggested by several theoretical cosmologists
(e.g., A. Friedmann [1922], G. Lemaitre [1927]). This expansion
is the observational basis of the *Big Bang theory. Essential to
the study of cosmic expansion is the accurate measurement of
intergalactic distances, and such measurement is dependent on the
use of "standard candles", astronomical objects whose intrinsic
brightness is known and whose distance can therefore be
calculated from apparent brightness. ... ... C.J. Hogan et al (3
authors at 3 installations, US CL) present a review of current
research on the temporal history of cosmic expansion, with
emphasis on recent work concerning the use of *type 1a supernovae
as standard candles. The authors make the following points: 1)
Until recently, the intrinsic brightness of all standard candles
used in observations has been found to be too variable, changing
with the evolution of the object or showing too much diversity
from one object to the other. However, during the past decade,
astrophysicists have been able to precisely determine the
intrinsic brightness of one kind of astronomical object, the type
1a supernova, and these objects have become the best calibrated
standard candles known to astronomers. Currently, observations of
type 1a supernovae are challenging decades of conventional ideas
concerning cosmic expansion. 2) Locating distant supernovae
involves taking images of the same part of the sky a few weeks
apart and searching for changes that might be exploding stars.
Because the digital light detectors can precisely count the
number of photons in each picture element, one makes a simple
subtraction of the first image from the second and looks for
significant differences from zero. With present equipment,
thousands of galaxies are checked in each image pair... After
supernovae candidates are located, the *Keck telescopes in
Hawaii, the largest optical instruments in the world, are pointed
at the objects, and critical observations establish whether or
not the objects discovered are in fact type 1a supernovae. The
observations are then used to gauge the intrinsic brightness of
the objects more exactly and to determine their redshifts... Two
teams have now studied a total of approximately 40 high redshift
supernovae, objects that erupted between 4 and 7 billion years
ago, when the universe was between one-half and two-thirds of its
present age. The results have been surprising: the supernovae are
fainter than expected. The difference is slight, the distant
supernovae on average only 25 percent dimmer than forecast, but
this result is enough to call long-standing cosmological theories
into question. The conclusion from the observations is that the
cosmic expansion is slowing less quickly than previously thought.
3) If the Universe is made of normal matter, gravity must
steadily slow the cosmic expansion. A reduced slowing, as
indicated by the supernovae measurements, implies that the
overall density of matter in the Universe is low... However, the
big surprise is that the observed supernovae are fainter than
predicted even for a nearly empty universe. Taken at face value,
the observations appear to require that expansion is actually
accelerating with time. This is consistent with the "vacuum
energy" embodied in Einstein's equations as the so-called
"*cosmological constant". Unlike ordinary forms of mass and
energy, the vacuum energy adds gravity that is repulsive and can
drive the Universe apart at ever increasing speeds. The authors
conclude: "Evidence for a strange form of energy imparting a
repulsive gravitational force is the most interesting result we
could have hoped for, yet it is so astonishing that we and others
remain suitably skeptical."
-----------
C.J. Hogan et al: Surveying space-time with supernovae.
(Scientific American January 1999)
QY: Craig J. Hogan, Univ. of Washington Seattle 206-543-8992.
-----------
Text Notes:
... ... *redshifted: Redshift (symbol: z) is a lengthening of the
wavelengths of electromagnetic radiation from a source caused
either by the movement of the source (Doppler effect) or by the
expansion of the universe (cosmological redshift). Redshift is
defined as the change in wavelength of a particular spectral line
divided by the unshifted wavelength of that line. Large redshifts
imply large radial velocities (which imply large distances,
according to current cosmological theory), but at redshifts
greater than about 0.2 there is a relativistic divergence from a
linear relation. A redshift of 4.0 corresponds to an object
receding with a radial velocity 92% that of the velocity of
light. The largest astrophysical redshifts so far observed are of
the order of z = 4.9.
... ... *Note #1: In the expansion model, it is the space between
widely separated objects that is expanding. Neighboring objects,
such as close pairs of galaxies, do not move apart because their
mutual gravitational attraction exceeds the effect of the
cosmological expansion. However, the distance between two widely
separated galaxies, or clusters of galaxies, will increase as the
Universe expands.
... ... *Big Bang theory: The Big Bang theory is the general
cosmological model that proposes that all matter and radiation in
the universe originated in an explosion at a finite time in the
past.
... ... *type 1a supernovae: Type 1a supernovae are believed to
be *white dwarf stars that have accreted enough matter from
another star to be pushed over a mass threshold and into a
thermonuclear explosion.
... ... *white dwarf star: White dwarf stars are extremely dense
and compact stars that have undergone gravitational collapse.
They are the final stage in the evolution of low-mass stars after
they have lost their outer layers. White dwarf stars are about
the size of Earth, but with a mass about that of the Sun.
... ... *Keck telescopes: The Keck telescopes are a pair of twin
telescopes at the W. M. Keck Observatory on Mauna Kea, HI US,
each with 10 meter mirrors, the pair constructed 1992-1996. The
installation is managed by the University of California (US) and
the California Institute of Technology (US).
... ... *cosmological constant: A mathematical term introduced by
Einstein into the equations of general relativity, the purpose to
obtain a solution of the equations corresponding to a "static
universe". The term describes a pressure (if positive) or a
tension (if negative) which can cause the Universe to expand or
contract even in the absence of any matter ("vacuum energy").
When the expansion of the Universe was discovered, Einstein
apparently began to regard the introduction of this term as a
mistake, and he described the cosmological constant as the
"greatest mistake of my life". But the term has reappeared as the
proposed source of apparent accelerated cosmic expansion.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 22Jan99
-------------------
Related Background:
COSMOLOGY: THE END OF THE OLD MODEL UNIVERSE
Cosmologists are apparently expecting the near-future necessity
for profound conceptual alterations in their field. Peter Coles
(University of London, UK) presents a short review of the current
situation and makes the following points: 1) Observations only
recently made possible by improvements in astronomical
instrumentation have put theoretical models of the Universe under
intense pressure. The standard ideas of the 1980s about the shape
and history of the Universe have now been abandoned -- and
cosmologists are now taking seriously the possibility that the
Universe is pervaded by some sort of "vacuum energy" whose origin
is not at all understood. 2) The weakness of the Big Bang model
is that the numerical values of certain essential parameters in
the model (the Hubble constant, the density parameter, and, in
some versions, the cosmological constant) are not predicted by
theory, and thus the parameters must be inferred from
observations. 3) The Big Bang model does not deserve to be called
a "theory" unless and until it can explain how nonuniformities of
galaxies and clusters of galaxies came into being and evolved. 4)
The Cold Dark Matter model of structure formation, first proposed
in the 1980s, is in serious difficulty because the consequent
significant gravitational brake on expansion is not evident, and
in fact expansion may be accelerating. Current observations
coupled with current dynamical arguments all suggest a global
density of matter in the Universe less than the value required to
make the Universe recollapse. 5) The existence of a cosmological
constant (or vacuum energy) of the required size necessary to
make the basic cosmological models work is not at all explained
by current theories of the fundamental interactions of matter. 6)
There is every reason to be confident that the important issues
will soon be resolved, because a data explosion is about to
engulf cosmology, a new generation of galaxy surveys. The Sloan
Digital Sky Survey, for example, will encompass more than a
million galaxies. The cosmological community is bracing itself
for the arrival of these enormous new data sets and the new
insights they will surely bring. 7) It is possible that none of
the available models will fit all the new data. Coles concludes:
"For many of us, that is the most exciting possibility of all, as
we would have to move to stranger theories, perhaps not even
based on General Relativity."
QY: Peter Coles [p.coles@qmw.ac.uk]
(Nature 25 Jun 98 393:741) (Science-Week 17 Jul 98)


3. THE DUSTY ATMOSPHERE OF A BROWN DWARF STAR
Brown dwarf stars are formed by the contraction of a lump of gas
with a mass too small for nuclear reactions to begin in the core.
Such a star has a relatively short-lived luminosity
(approximately 100 million years) as the result of conversion of
gravitational energy to radiation. The surface temperature of a
brown dwarf is below 2500 degrees kelvin. As recently as 1994,
brown dwarfs were "theoretical" stars, with no brown dwarfs
considered to be unambiguously identified. Since 1994, however, a
number of brown dwarf stars (and what appear to be large planets)
have been identified. ... ... C.A. Griffith et al (3 authors at 3
installations, US) now report observations of the brown dwarf
star Gliese 229B, which exhibits certain unique characteristics.
At 900 degrees kelvin, the atmosphere of this object is too warm
to contain ice clouds like those on Jupiter and too cool to
contain silicate clouds like those on low-mass stars. These
unique conditions (high gravity and the lack of high clouds)
permit spectroscopic visibility of the atmosphere down to higher
pressures (i.e., closer to the surface) than possible in cool
stars or planets. The authors investigated the structure of the
atmosphere of Gliese 229B by analyzing its optical spectrum in
the interval 0.85 to 1.0 micron, the spectrum obtained at the
*Keck 1 telescope. The authors report that the spectrum of Gliese
229B indicates deep-atmosphere particulate matter with the
optical properties of neither ice nor silicates. The authors
suggest the reddish color of the particles indicates an organic
composition characteristic of aerosols in planetary
stratospheres, and that the *mass fraction of the particles
agrees with a photochemical origin involving incident radiation
from its companion primary star (Gliese 229A).
-----------
C.A. Griffith et al: The dusty atmosphere of the brown dwarf
Gliese 229B.
(Science 11 Dec 98 282:2063)
QY: Caitlin A. Griffith, Northern Arizona University 520-523-5511
-----------
Text Notes:
... ... *Keck 1 telescope: The Keck telescopes are a pair of twin
telescopes at the W. M. Keck Observatory on Mauna Kea, HI US,
each with a 10 meter mirror, the pair constructed 1992-1996. The
installation is managed by the University of California (US) and
the California Institute of Technology (US).
... ... *mass fraction: The mass fraction of aerosols is related
to the *eddy diffusion coefficient k, the mass density of the
atmosphere d, the net mass flux f, and the scale height of the
atmosphere h according to F = fh/kd.
... ... *eddy diffusion coefficient: (turbulent diffusion
coefficient) The exchange coefficient for the diffusion of a
conserved property by eddies in a turbulent flow. In general, an
"eddy" is a vortex-like motion of fluid running contrary to the
main current.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 12Feb99
-------------------
Related Background:
GIANT PLANETS VS. BROWN DWARFS
Filipe D. Santos (Centro de Fisica da Universidade de Lisboa, PT)
presents a short review of current ideas concerning giant
extrasolar planets and *brown dwarf stars. The author makes the
following points: 1) The recent discoveries of planets orbiting
nearby Sun-like stars have revealed that planetary systems can be
surprisingly diverse. The initial discovery in 1995 of the planet
around the star 51 Pegasi was a surprise because it is apparently
a planet with mass about that of Jupiter (at least 0.44 Jupiter-
mass) and an orbital period of only 4.2 days, which implies that
the planet is 20 times closer to its star than Earth is to the
sun. 2) Seven additional planets around solar-type stars have
since been discovered, with Jupiter-mass values ranging from 0.44
to 6.84. 3) Two critical questions are, a) Where should we set
the dividing line that distinguishes massive planets from brown
dwarfs? and, b) What are the mechanisms leading to the formation
of massive planets and brown dwarfs? 4) Brown dwarfs are expected
to have masses smaller than the hydrogen-burning limit of
approximately 0.075 solar-mass (approximately 75 Jupiter-mass),
but probably larger than the deuterium-burning limit of 0.013
solar-mass (approximately 13 Jupiter-mass). 5) Like the companion
massive planets mentioned, several companion brown dwarfs to
solar-type stars have also been identified. One method of
investigating brown dwarfs involves *astrometric measurements,
and in all cases of brown dwarfs investigated by the astrometric
method, the masses are above or very close to the hydrogen-
burning limit. The extant data thus suggest that the distribution
of mass of brown dwarfs does not extend to masses as small as
giant planets. Also, the new measurements indicate that brown
dwarfs orbiting solar-type stars are very rare. 6) The discovery
of Jupiter-mass planets with orbits very close to their stars
poses a considerable problem, because it is difficult to
understand how such planets could form in place. (Five known
Jupiter-mass planets have orbital radii smaller than the distance
from Mercury to the Sun.) The suggestion has been made that these
planets formed at larger distances and migrated inward, but the
proposed migration mechanisms are not yet empirically
distinguishable. The author concludes: "Clearly the discovery of
planetary systems outside our solar system has opened a Pandora's
box of startling phenomena and new questions."
QY: Filipe D. Santos [fdsantos@milkyway.cii.fc.ul.pt]
(Science 17 Jul 98 281:359) (Science-Week 31 Jul 98)
-----------
Text Notes:
... ... *brown dwarf stars: See previous report.
... ... *astrometric measurements: This method of detection
infers the presence of a companion to a star by measuring the
position of the star as it orbits the center of mass of the
entire system. From the orbital inclination, the real mass of the
companion can be derived.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 31Jul99


4. ON HEAT SHOCK PROTEINS
In a multicellular organism, the differentiation of structure and
function among various types of cells depends on which genes in
the genome are activated. Every cell in an organism carries the
same genome, but the set of operating genes differs from cell
type to cell type. One central question, therefore, is how are
genes selected for activation? In bacteria, groups of related
genes are organized into "operons" whose *transcription is
regulated by repressor and/or regulator proteins that bind to
specific DNA sequences. But operons have not been found in
*eukaryotes. However, DNA sequences that play a role in
regulating the transcription of genes in response to specific
signals have been identified near the *transcriptional start
sites of various eukaryotic genes. Because these sequences allow
transcription to be regulated in response to a particular type of
signal, they are referred to as "response elements". Placement of
the same response element next to genes residing at different
locations allows the transcription of such a group of genes to be
regulated by the same signal even though the genes are not
adjacent to each other. One of the first DNA response elements to
be identified is a nucleotide sequence that coordinates the
activity of genes whose products protect organisms against
excessive heat. If cells growing in culture are briefly warmed by
raising the temperature a few degrees, the transcription of
several "heat-shock" genes is activated. It has been found that
if a heat-shock response element can be identified, relocation of
that response element (by genetic engineering) to a gene which is
not normally a heat-shock gene will turn that gene into a heat-
shock gene. Experiments have revealed that the activation of
heat-shock genes is mediated by the binding of a protein called
the "heat-shock transcription factor" to the heat-shock response
element. The heat-shock transcription factor is apparently
present in an inactive form in non-heated cells, but elevation of
temperature causes a change in the structure of the protein, and
this change allows the protein to bind to the heat-shock response
element in DNA. What is most important about the regulation of
heat-shock genes is that the basics of this regulation are
apparently involved in the regulation of other eukaryotic genes,
and as a result the molecular biology of heat-shock proteins has
become a paradigm useful for the understanding of eukaryotic gene
regulation. ... ... Richard I. Morimoto (Northwestern University,
US) presents a review of current research concerning the
regulation of the heat-shock trancriptional response, the author
making the following points: 1) In stressed environments,
proteins can unfold, misfold, or aggregate. The heat-shock
response, through the elevated synthesis of *molecular chaperones
and *proteases, repairs protein damage and assists in the
recovery of the cell. 2) The induction of transcription of heat
shock genes is a response to a number of stress signals,
including environmental stresses, certain non-stress conditions,
and various disease states. Although changes in heat-shock
protein expression have been associated with certain diseases, it
is not clear whether the changes are an adaptation to the
particular disease state, a reflection of the suboptimal cellular
environment associated with the disease state, or a signal
warning other cells and tissues of imminent danger. 3) The
protective role of heat-shock proteins is a measure of their
capacity to assist in the repair of protein damage. Whether in
*prokaryotes, plants, or animals, overexpression of one or more
heat-shock proteins is often sufficient to protect cells and
tissues against otherwise lethal exposure to diverse
environmental stresses (e.g., hydrogen peroxide and other
oxidants, toxic chemicals, extreme temperatures, ethanol-induced
toxicity). In vertebrate tissue culture cells and animal models,
elevating the population of heat-shock proteins by various
methods restricts or substantially reduces the level of pathology
and cell death following environmental stress. This has led to
the recognition that heat-shock proteins, via their chaperoning
effects on other proteins, protect cells from many forms of
stress-induced cell damage and can influence the course of
disease states. 4) Future studies will establish how different
members of the heat-shock transcription factor gene family either
respond to different forms of stress, ensure regulation of
distinct stages of activation or repression of the heat-shock
response, or provide an interface between the stress response and
other transcription regulatory pathways.
-----------
Richard I. Morimoto: Regulation of the heat shock transcriptional
response: cross-talk between a family of heat shock factors,
molecular chaperones, and negative regulators. 
(Genes & Development 15 Dec 98 12:3788)
QY: Richard I. Morimoto [r-morimoto@nwu.edu] Fax: 847-491-4461
[Editor's note: The review contains over 100 titled references.]
-----------
Text Notes:
... ... *transcription: Transcription is the process by which the
genetic information in DNA is converted into RNA, and
transcription factors are a class of DNA-binding proteins that
regulate RNA transcription. Transcription factor genes are simply
the genes that code for the transcription factor proteins.
... ... *eukaryotes: Cells (and organisms consisting of such
cells) that contain intracellular membrane-bound compartments
such as a nucleus (membrane-bound "organelles"). Prokaryotes are
unicellular or filamentous organisms in which cells lack internal
membrane compartments such as a nucleus. E.g., bacteria.
... ... *transcriptional start sites: (transcription start
points) In this context, a start site or start point is the base
pair in DNA at which the first nucleotide is incorporated into an
RNA transcript. It is most often a purine, and in many cases is
the central base in the sequence cytosine-adenine-thymine. The
term "start site" should not be confused with "start codon",
which is the trinucleotide adenine-uracil-guanine that codes for
the first amino acid residue in the synthesis of all prokaryotic
and mitochondrial proteins.
... ... *mitochondrial proteins: Mitochondria are organelles of
the cell cytoplasm, and the principal energy source of the
cell. They contain various enzymes involved in electron transport
and metabolic cycles.
... ... *molecular chaperones: In general, chaperone proteins are
proteins required for the proper folding and/or assembly of
another protein or protein complex. 
... ... *proteases: A protease is an enzyme that splits proteins
and thereby degrades them.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 12Feb99


5. A HYDROGENOSOME WITH A GENOME
Certain *anaerobic *protozoa and *fungi possess membrane-bound
organelles known as "hydrogenosomes". These organelles are
approximately 1 micron in diameter and are so called because they
produce molecular hydrogen. The anaerobic *ciliate protozoan
Nyctotherus ovalis, found in the hindgut of several species of
cockroach, has numerous hydrogenosomes that are intimately
associated with *endosymbiotic methane-producing *Archaea, the
latter using the hydrogen produced by the hydrogenosomes. Like
*mitochondria, the hydrogenosomes are bound by distinct double
membranes and have an inner membrane with *cristae-like
projections. The matrix contains *ribosome-like particles of the
same size as a numerous type of ribosome (70s) of the
endosymbiotic methanogenic Archaea. It has been postulated that
hydrogenosomes evolved from mitochondria by the concomitant loss
of their respiration and organellar genomes, and indeed so far no
hydrogenosome has been found that has a genome.
... ... A. Akhmanova et al (8 authors at 2 installations, NL) now
report evidence of a hydrogenosomal genome of apparent
mitochondrial descent, and also evidence that the protozoan N.
ovalis possesses a new type of nucleus-encoded "iron-only"
*hydrogenase. The authors suggest their results indicate that N.
ovalis hydrogenosomes evolved from mitochondria, but that
contrary to what has been proposed by others, the hydrogenosomes
have not relinquished their genomes. The authors further suggest
that the evolutionary origin of the N. ovalis nuclear hydrogenase
gene remains puzzling.
-----------
A. Akhmanova et al: A hydrogenosome with a genome.
(Nature 10 Dec 98 396:527)
QY: Johannes H.P. Hackstein [hack@sci.kun.nl]
-----------
Text Notes:
... ... *anaerobic: Refers to a life form or process sustained in
the absence of free (gaseous or dissolved) oxygen.
... ... *protozoa: A phylum (or subkingdom) comprising
unicellular and colonial animals of varied form, cells ranging
from simple to extremely complex macro-structures.
... ... *fungi: A kingdom of primarily multicellular organisms
lacking chlorophyll and existing as parasites, symbionts, or
saprophytes. In general, "symbionts" are organisms that live in
close association (symbiosis) with other organisms; saprophytes
are organisms that feed on dead or decaying life forms.
... ... *ciliate: Cilia are short threadlike extensions, hundreds
usually present on an individual ciliated cell, the cilia
undergoing synchronized movements to produce locomotion of the
protozoan.
... ... *endosymbiotic: Endosymbiosis is an arrangement in which
one organism lives inside another organism, but the term is
usually restricted to arrangements of mutual benefit, thus not
including parasite-host relationships. A number of eukaryotic
cell organelles (including mitochondria) are believed to have
originated from endosymbiotic relationships between eukaryotic
cells and simpler cells.
... ... *Archaea: The archaebacteria (also called the Archaea)
are a subkingdom of bacteria considered to be ancient compared to
other bacterial kingdoms, and possibly the most ancient life
forms and the ancestors of all eukaryotes (cells and organisms
with intracellular membrane-bound organelles). They typically
exist in extreme environments, and include the methane-producing
bacteria (methanogens), the "salt-loving" bacteria (halophilic
bacteria), and the sulfur-acid tolerant thermoacidophilic
bacteria.
... ... *mitochondria: Mitochondria are double-membrane enclosed
organelles of cells that are involved with several important
biochemical pathways, including electron transport and oxidative
metabolism.
... ... *cristae: The folds of the inner mitochondrial membrane.
They contain the enzymes and other proteins involved in
mitochondrial metabolism.
... ... *ribosome: A ribosome (not to be confused with riboZYME)
is a small particle, a complex of various ribonucleic acid
component subunits and proteins that functions as the site of
protein synthesis.
... ... *hydrogenase: (hydrogenlyase) An enzyme that catalyzes
the interaction of reduced *ferredoxin with ionic hydrogen to
produce oxidized ferredoxin and molecular hydrogen. 
... ... *ferredoxin: In general, a simple non-enzymic iron-sulfur
protein. Such proteins act as electron carriers in a variety of
oxidation-reduction systems and are found in a wide range of
microorganisms, in chloroplasts, and in some types of
mitochondria.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 12Feb99
-------------------
Related Background:
GENOME OF THE TYPHUS PARASITE AND THE ORIGIN OF MITOCHONDRIA
The Rickettsia are small bacteria (600 x 300 nanometers, or
spherical as "cocci"), classified as a type of proteobacteria
(i.e., "purple" bacteria, a huge phylum including many common
bacteria). The Rickettsia are obligate intracellular parasites
(i.e., they can replicate only inside living cells), and one of
the most notorious of these parasites is R. prowazekii, the agent
of epidemic louse-born typhus in humans. R. prowazekii is
estimated to have infected 20 to 30 million humans in the wake of
the First World War and killed another few million humans
following the Second World War. Because it is apparently the
descendent of free-living organisms, the genome of R. prowazekii
may provide insight into the adaptations producing an obligate
intracellular lifestyle. Also, phylogenetic analyses based on
sequences of *ribosomal RNA and *heat-shock proteins indicate
that *mitochondria may be derived from the proteobacteria, and
indeed the closest extant relatives of the ancestor to
mitochondria seem to be the Rickettsia. Finally, the genome of R.
prowazekii is a small one, making it amenable to genome analysis.
... ... S.G.E. Andersson et al now report the complete genome
sequence (1,111,523 *base pairs) of R. prowazekii. The authors
report this genome contains 834 protein-coding genes, the
functional profiles of which show similarities to those of
mitochondrial genes: no genes required for anaerobic glycolysis
are found in either R. prowazekii or mitochondrial genomes, but a
complete set of genes encoding components of the *tricarboxylic
acid cycle and the *respiratory-chain complex is found in R.
prowazekii (and in mitochondria). In effect, *ATP production in
Rickettsia is the same as that in mitochondria. Many genes
involved in the biosynthesis and regulation of biosynthesis of
amino acids and *nucleosides in free-living bacteria are absent
from R. prowazekii and mitochondria, and such genes have
apparently been replaced by homologues in the host genome. The R.
prowazekii genome contains the highest proportion of non-coding
DNA (24 percent) detected so far in a microbial genome, and the
authors suggest such non-coding sequences may be *degraded
remnants of "neutralized" genes that await elimination from the
genome. The authors finally suggest that phylogenetic analyses
indicate that R. prowazekii is more closely related to
mitochondria than is any other microbe studied thus far.
-----------
S.G.E. Andersson et al (10 authors at 2 installations, SE US)
The genome sequence of Rickettsia prowazekii and the origin of
mitochondria.
(Nature 12 Nov 98 396:133)
QY: Charles G. Kurland [chuck@xray.bmc.uu.se]
-----------
Text Notes:
... ... *ribosomal RNA: A class of RNA molecules that have an
important role in the structure of ribosomes, the large molecular
entities that carry out protein synthesis in all cells.
... ... *heat-shock proteins: A group of specific proteins
apparently synthesized by both prokaryotes (cells without
membrane-bound organelles) and eukaryotes (cells with membrane-
bound organelles) in response to a sudden elevation of ambient
temperature.
... ... *mitochondria: Mitochondria are double-membrane enclosed
organelles of cells that are involved with several important
biochemical pathways, including electron transport and oxidative
metabolism. Various types of eukaryotic cells may contain from a
few to several thousand mitochondria in each cell type. The
mitochondria are relatively large cylindrical structures up to 10
microns long and up to 2 microns in diameter, and most biologists
believe mitochondria are cell organelles that may have originated
as separate organisms that became resident in eukaryotic cells.
Mitochondrial DNA is independent of nuclear DNA. It consists of a
circular molecule, 16,569 base pairs long in humans, with a known
nucleotide sequence.
... ... *base pairs: The term "base pair" refers to the bases
(nucleotides) always found chemically bonded together in the DNA
double helix (adenine, for example, always bonds with thymine,
and guanine with cytosine).
... ... *tricarboxylic acid cycle: (Krebs cycle, citric acid
cycle) In aerobic respiration, the set of oxidative reactions
occurring after *glycolysis.
... ... *glycolysis: One of the 2 main energy-producing pathways
of the cell, this involves the anaerobic breakdown of glucose
with the generation of 2 molecules of adenosine triphosphate
(*ATP).
... ... *respiratory-chain complex: (electron transport chain)
Refers to a sequence of steps in the final stage of the aerobic
respiration biochemical pathway in which high energy electrons
are effectively passed through a series of membrane-bound carrier
molecules to support a proton gradient involved in energy
storage. The term "transport" here refers essentially to a
chemical flow diagram and not necessarily to an actual spatial
translocation of electrons.
... ... *ATP: (adenosine triphosphate) ATP 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.
... ... *nucleosides: The base-sugar moieties of nucleotides.
... ... *degraded remnants: In this context, the idea is that the
Rickettsia are descendents of bacteria with substantially larger
genomes, and that both Rickettsia and mitochondria are the
products of several types of reductive evolution.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 18Dec98


6. ON MODELS OF IMMUNE MEMORY
Higher vertebrates, including humans, have through evolution
developed an immune system that can selectively destroy or
inactivate foreign molecules and foreign cells (*antigens)
without harming the molecules or normal cells of the host. The
vertebrate immune system apparently retains a "memory" of each
antigen attack, allowing the immune system to respond more
efficiently the next time it encounters the same invader. One
group of immune system cells involved in this immune system
memory is a small fraction of the proliferating *B-lymphocyte
cell population, the fraction effectively set aside as a reserve
population of cells to be directed against a specific stimulating
antigen. Such cells, called "memory B cells", are
indistinguishable in appearance from other unstimulated
lymphocytes and like them do not secrete antibody. But if the
organism is exposed to the same antigen a second time, the
reserve population of antigen-specific memory cells quickly
proliferates and differentiates into antibody-secreting plasma
cells, thereby allowing what is called the "secondary response"
to a given antigen to occur more rapidly and produce more
antibody than the initial or "primary response". The
effectiveness of the secondary response is the apparent reason
why humans, for example, rarely contract such diseases as chicken
pox or mumps more than once. One of the central problems in
immunology is to provide a molecular explanation for immune
system memory (also called "immune memory). There has been much
debate concerning the relative contributions to immune memory of
processes such as the persistence of antigens, *cross-reactive
stimulation, *homeostasis, competition between different lineages
of lymphocytes, and the rate of cell turnover
... ... R. Antia et al (3 authors at 2 installations, US) present
several mathematical models designed to investigate the
contributions of the various processes to the longevity of immune
memory. The authors define immune memory as the maintenance of an
elevated population of antigen-specific cells, and they define
the longevity of immune memory as the rate of decline of the
population of antigen-specific memory cells. The models presented
by the authors incorporate a repertoire of immune cells, each
lineage with distinct antigenic specificities, the basic
equations describing the dynamics of individual lineages and the
total population of cells. The authors suggest their results
indicate that if homeostatic control regulates the total
population of memory cells, then immune memory will be long-lived
(half-life > 1 year). The authors also suggest that the longevity
of immune memory in this situation will be insensitive to the
relative rates of cross-reactive stimulation, the rate of
turnover of immune cells, and the functional form of the
mathematical term for the maintenance of homeostasis. Further,
the authors suggest their models predict that when the frequency
of antigenic stimulation from other infectious agents is very
high, the duration of immune memory is likely to be relatively
low: i.e., sufficiently frequent exposure to new pathogens will
result in a relatively high rate of decline of immune memory with
respect to a given pathogen.
-----------
R. Antia et al: Models of immune memory: On the role of cross-
reactive stimulation, competition, and homeostasis in maintaining
immune memory.
(Proc. Natl. Acad. Sci. US 8 Dec 98 95:14926)
QY: Rustom Antia [rantia@biology.emory.edu]
-----------
Editor's note: In addition to the background material below, see
the SW Focus Report "Immunology: Biological and Medical Aspects"
at URL [http://scienceweek.com/swfr037.htm]
-----------
Text Notes:
... ... *antigens: In general, an antigen is any entity that
provokes an immune response, and this includes, in certain
disease states, entities that are not "foreign" to the body.
... ... *B-lymphocyte cell: Lymphocytes (lymph cells, lympho-
leukocytes) are a type of leukocyte (white blood cell)
responsible for the immune response. In general, there are two
classes of lymphocytes: 1) the B-cells, when presented with a
foreign chemical entity (antigen), change into antibody producing
plasma cells; 2) the T-cells interact directly with foreign
invaders such as bacteria and viruses.
... ... *cross-reactive stimulation: In general, in this context,
a "cross-reaction" is an immunological phenomenon in which an
antigen reacts with an antibody that has been raised (produced)
against a different antigen. The term "cross-reactive
stimulation" refers to the production of cross-reacting antibody
(or immune cell), i.e., an antibody (or immune cell) able to
react with an antigen that did not specifically stimulate its
original production.
... ... *homeostasis: The term "homeostasis" refers to a
physiological equilibrium necessary in general for the viability
of an organism, and in particular for the operation of many
cellular functions. Homeostatic mechanisms in biological systems
usually involve an element of negative feedback signaling. In
vertebrates, for example, when blood temperature is too high,
temperature receptors provoke a sequence of events involving many
pathways that ultimately results in a lowering of body temper-
ature. Similar homeostatic mechanisms operate at cellular levels.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 12Feb99
-------------------
Related Background:
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 [david.schatz@yale.edu]
-----------
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 [http://scienceweek.com] 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.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 21Aug98
-------------------
Related Background:
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)


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Here are the titles of all the current free Focus Reports
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Microbial Drug Resistance
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Science and Commerce in Conflict
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Scientific Information Distribution
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