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 19, 1999 -- Vol. 3 Number 8

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

Every great scientific truth goes through three
stages. First, people say it conflicts with the Bible.
Next they say it had been discovered before. Lastly
they say they always believed it.
-- Louis Agassiz (1807-1873)

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

Contents of This Issue:

1. On the Angiostatin-Endostatin-Entremed Bubble
2. On Quantum Non-Demolition Measurements in Optics
3. Eight Calves Cloned from Somatic Cells of a Single Adult
4. On DNA Microsatellites
5. Elevating Vitamin E Content of Plants via Genetic Engineering
6. A Cellular Receptor for Three Different Pathogens
7. Early Physiological Abnormalities in SIV Infection

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

1. ON THE ANGIOSTATIN-ENDOSTATIN-ENTREMED BUBBLE
In May of 1998 [see background material below] a front-page
article in _The New York Times_ reported a "breakthrough" in
cancer research, the breakthrough involving two drugs called
"angiostatin" and "endostatin" developed by Judah Folkman
(Harvard University, US) and licensed to Entremed Inc., a startup
biotechnology company. _The New York Times_ article produced a
media and financial bubble that in turn provoked considerable
criticism of both _The New York Times_ and the author of the
article. A new chapter in the brouhaha has now evidently
appeared: The Bristol-Meyers Squibb Company, the world's largest
manufacturer of cancer drugs, has announced it has abandoned its
agreement with Entremed Inc. to develop the drug angiostatin
because Bristol-Meyers no longer considers the compound a good
candidate for human tests. The stock of Entremed immediately (10
Feb 99) fell 47 percent (current share price US$12.9). Two days
after this announcement (12 Feb), it was reported that the US
National Cancer Institute has announced that its researchers have
finally duplicated some of the results obtained by Folkman with
the drug endostatin. Three months ago, the same institute
publicly announced that they could not reproduce Folkman's work.
James M. Pluda, a senior clinical investigator at the cancer
institute, is quoted as follows: "Lots of drugs have had great
activity in mice and then have not worked in people... It's very
premature to extrapolate from mouse data that this drug
[endostatin] will have the same activity in people that the mouse
version had in mice in Folkman's lab. We need careful clinical
trials to evaluate whether this drug will have any activity at
all." As expected, following the new cancer institute
announcement, the stock of Entremed regained the loss of the
previous days. Meanwhile, Entremed has announced that it has
licensed a new company to produce large quantities of
angiostatin, the drug rejected by Bristol-Meyers. These new
events provide another chapter in this story, the details of
which are found in the background material below. As specialists,
most biologists are perhaps fully aware of the many hurdles
between laboratory research and clinical applications. For people
outside the biology community, this might be a cautionary tale.
In any case, the saga of angiostatin and endostatin is apparently
not yet finished.
-----------
(New York Times 11 Feb 99) (New York Times 12 Feb 99)
-------------------
Summary by SCIENCE-WEEK [http://scienceweek.com] 19Feb99
-------------------
Related Background:
SCIENCE NEWS, STOCK PRICES, AND BOOK DEALS
     A cogent example of the interaction of science, medicine,
the media, the stock market, and personal riches came into public
view recently. The sequence of events in this episode was
apparently as follows:
     1) On Sunday, May 3, 1998, _The New York Times_ ran a front
page story by Gina Kolata, one of the chief science writers of
_The New York Times_, and a reporter who has been writing about
science for at least 30 years. The story concerned the two
chemicals angiostatin and endostatin that have been known for
some time to block angiogenesis in tumors in mice (see background
material following this report). The chemicals have never been
tested in humans, they are not the only chemicals that achieve
this effect, and they are not available as "drugs" that can be
administered by a physician. But the thrust of the story was that
this was new information, the headline, "A Cautious Awe Greets
Drugs That Eradicate Tumors in Mice." The story quoted Nobel
Laureate James Watson as telling Kolata that Judah Folkman, one
of the primary researchers in the field of anti-angiogenesis
chemicals, "will cure cancer within 2 years" and "will be
remembered along with scientists like Darwin as someone who
permanently altered civilization. Kolata also reported that
Richard Klausner, director of the US National Cancer Institute
said the two chemicals were "the single most exciting thing on
the horizon" for the treatment of cancer, and that they were the
top priority of the National Cancer Institute.
     2) On the afternoon of the same day the story was published
in _The New York Times_, a New York book agent named John
Brockman telephoned reporter Gina Kolata about the story and
apparently told her he could get her a US$2 million advance for a
book on the subject. Kolata immediately began writing a book
proposal, and sent the proposal via Email to Brockman within
hours.
     3) That evening, all major television networks highlighted
the story that had appeared in _The New York Times_. Brockman
sent the proposal to New York publishers at midnight of that
first day, following the network news reports.
     4) At 9:30 the next morning (Monday), Brockman informed
Kolata that he already had the first offer from a major New York
publishing house.
     5) Also on Monday morning, the stock of EntreMed Inc. (US),
the company that holds the rights to turn the two chemicals
angiostatin and endostatin into drugs, rose immediately from a
previous Friday closing of US$12 a share to a Monday morning
opening at US$83 a share.
     6) Also beginning Monday morning, oncologists and other
physicians around the country found themselves deluged with
inquiries from cancer patients, many of whom were saying they
would be putting off chemotherapy to wait for the new drugs.
     7) By the end of the week, the bubble had completely burst:
Other reporters published stories revealing the chemicals named
in the May 3rd _New York Times_ story were already well-known,
tested only on mice, and not available at all as drugs. Both
Watson and Klausner backed off from their reported comments,
saying they had been misinterpreted. The price of EntreMed shares
fell back to $30. Kolata withdrew her revealed book proposal
after a discussion with her editors, and the agent Brockman
already had a substitute deal in the works for a book on the
subject by a reporter at another newspaper. Finally, around the
country, physicians had the task of explaining to their patients
that no, a miracle cancer cure was not yet available.
     As expected, much is being written about this episode, with
one question in the minds of many people: Why does this happen?
Well, one reason why it happens is that these days news editors
are prone to present features to their readers as "news". This
was a feature article, and it should have appeared as an article
in a magazine, and not on the front news page of _The New York
Times_.
     Secondly, the habit that reporters have of using direct
sound-bite quotes from scientists to bolster the apparent
importance of their stories too often produces misinformation,
inappropriate emphasis, and whatnot, and certainly there is a
tendency to avoid quotes that reduce the significance of the
"news". Science-news reporting propped and hyped to be "exciting"
does a disservice to the public and can be dangerous as well. The
James Watson comment, apparently, actually occurred during a
conversation Kolata had with Watson _two months before_ at a
dinner table.
     In summary, this so-called news story should never have
appeared in the first place as "news", should never have included
quotes from scientists with the quotes deliberately used to hype
the material beyond any significance attributed by specialists,
should never have been used as a prop for a quick lucrative book
deal, should never have been reported the way it was by
television broadcasters. The media, and in particular _The New
York Times_, have been deservedly embarrassed by this episode,
and the credibility of science-reporting by _The New York Times_
has been seriously and unfortunately compromised.
     [Editor's note: concerning the science, we are appending
here several relevant reports from past issues of SCIENCE-WEEK.
The reader will observe that the anti-angiogenesis chemical
endostatin was already noted here in December 1997.]
(Science 15 May 98 280:996) (Science-Week 5 Jun 98)
-------------------
Related Background:
CANCER TREATMENT BY TARGETING TUMOR BLOOD VESSELS
Bacteriophage (phage) is a virus type that infects bacteria, and
it has been useful as a cloning vector in genetic engineering.
The phage injects its own DNA into the bacterium, effectively
assuming enough control of the bacterial genome to replicate
itself, with the ultimate disintegration of the bacterium and
liberation of the phage clones. A "phage library" is a collection
of genomic DNA fragments, each contained in a bacteriophage
cloning vector and propagated by infection of a host bacterium
(usually E. coli). The essential idea, in the context of this
report (and in many other research efforts), is to use the
genetic machinery of the phage to control the metabolic machinery
of the bacterium to produce (synthesize) particular complex
biomolecules (such as polypeptides) needed for testing. "Nude
mice" are a genetic variant of laboratory mice lacking a thymus
gland, which means they are unable to produce the T-cells
(Thymus-cells) necessary for various aspects of the mammalian
immune response. The origin and development of tumor blood
vessels (angiogenesis), is an important consideration in the
growth of cancerous tumors, since the tumor provokes directed
angiogenesis into itself with the end result that the tumor is
supplied with oxygen and nutrients. Without angiogenesis, tumors
can attain only a small size before becoming self-inhibiting. A
"xenograft" is a graft of tissue from one species into the body
of another species. ... ... Arap et al (3 authors at Burnham
Institute, US) report the use of in vivo selection of phage
libraries to isolate peptides that home specifically to tumor
blood vessels. When coupled to the anticancer drug doxorubicin,
two peptides were found that enhance the efficacy of the drug
against human breast cancer xenografts in nude mice and also
reduced the toxicity of the drug. The authors suggest their
results indicate it may be possible to develop targeted
chemotherapy strategies based on selective expression of
receptors in tumor blood vessels.
QY: Erkki Ruoslahti [ruoslahti@burnham-inst.org]
(Science 16 Jan 98) (Science-Week 30 Jan 98)
-------------------
Related Background:
CANCER: NO ACQUIRED DRUG RESISTANCE TO ANTI-ANGIOGENIC AGENT
Angiogenesis is the generation of new blood vessels, a controlled
sequence of cell differentiation and tissue formation programmed
by the genome. It is of obvious importance during embryological
development, since new tissues need a blood supply in order to
continue macroscopic growth, and the angiogenesis process is also
of great importance during tissue trauma repair. Like new
embryological tissue, a neoplasm (a tumor) also needs a blood
supply, and one of the characteristics of tumor growth is the
provocation of angiogenesis by the cancer cells so that the mass
of such cells becomes supplied with adequate vascularization. It
is known, for example, that tumors will not grow beyond a few
millimeters in diameter in the absence of a newly forming blood
supply. Cancer cells apparently provoke angiogenesis by secreting
growth factor substances, and if this is prevented, tumor growth
will be severely limited. But attempts to chemically interfere
with the secretion of growth factors by cancer cells usually fail
because the high proliferation rate of cancer cells ultimately
results in drug resistance produced by a mutational selection
process. However, the normal epithelial tissue involved in
angiogenesis is not rapidly mutating. Recently, a substance named
endostatin, a 20,000 molecular weight fragment of a type of
collagen, has been found to be a specific inhibitor of
endothelial cell proliferation (which means also of new blood
vessel growth), and it was found that endostatin effects only
proliferating endothelial cells, not resting cells, and not
normal, transformed, or neoplastic cells. It has been shown that
systemic administration of endostatin to tumor bearing mice
results in the regression of tumors to a microscopic size, and
one important question has been whether drug resistance to
endostatin would develop. ... ... Now Boehm et al (4 authors at
Harvard Univ., US) report that endostatin causes three tumor
types in mice to regress without the production of drug
resistance, and that repeated cycles of anti-angiogenic therapy
are followed by prolonged tumor dormancy without further therapy.
The authors suggest that angiogenesis inhibitors that do not
induce drug resistance may be valuable for long-term maintenance
therapy. This is important work, and one expects much will be
heard about endostatin in the future.
QY: Thomas Boehm [boehm_t@a1.tch.harvard.edu]
(Nature 27 Nov 97) (Science-Week 19 Dec 97)
-------------------
Related Background:
MOLECULAR TARGET OF ANTI-ANGIOGENESIS COMPOUNDS DISCOVERED
... Any clinically useful anti-angiogenesis compound is of
great interest to cancer specialists (oncologists). There are 10
or so anti-angiogenesis agents presently undergoing clinical
trials. One of these (TNP-470) is a derivative of the natural
fungal product fumagillin, whose anti-angiogenesis activity was
first discovered in 1985. Now the cellular target of fumagillin
and TNP-470 has been discovered, a specific protein which appears
to play an important role in the proliferation of endothelial
cells, the cells that line blood vessels. The work was reported
by Craig M. Crews et al (Yale University, US), who suggests the
identification of this protein target will open new avenues of
research for the understanding of tumor-induced
neo-vascularization. The results have been independently
confirmed by Jun O. Liu et al (Massachusetts Institute of
Technology, US).
(Proc. U. S. National Academy of Sciences, 94:6099 1997)
(Chemistry & Biology June 1997) (Science-Week 26 Jun 97)


2. ON QUANTUM NON-DEMOLITION MEASUREMENTS IN OPTICS
In quantum mechanics, a demolition measurement is any measurement
that alters the value of the physical observable being measured.
... ... P. Grangier et al (3 authors at 2 installations, FR)
review some of the theoretical and practical considerations
concerning attempts to achieve non-demolition measurements in
optics, the authors making the following points: 1) One of the
fundamental ideas in quantum mechanics is that a precise
measurement in the microscopic domain is not possible without the
introduction of a perturbation or "back action" inherent to the
very fact of measurement. This principle, known since the 1930s,
can be directly related to Heisenberg's uncertainty relations.
The connection arises from the fact that quantum formalism
describes physical quantities as non-commuting operators, i.e.,
mathematical objects (e.g., A and B) such that AB does not equal
BA [*Note #1]. The Heisenberg inequalities state that the product
of the uncertainties in A and B has a lower bound, the result of
which is that a very small change in the uncertainty of A will be
associated with a large change in the uncertainty of B. Although
this does not restrict directly the precision in the measurement
of A itself, the large fluctuations induced in B may eventually
couple back to A, which will then also be perturbed. This
measurement "back action" has far-reaching consequences from a
practical point of view, since it may prevent the retrieval of
the initial result is a series of repeated measurements. 2) In
the 1970s, in response to the problem of measurement "back
action", Braginsky, Thorne, Unruh, Caves and others introduced
the idea of "quantum non-demolition" measurement. This concept
involves choosing a measurement strategy to evade the undesirable
effect of back action. The key idea is to devise measurement
schemes in which the back-action noise is kept entirely within
unwanted observables without being coupled back onto the
quantities of interest. This quantity then remains uncontaminated
by the measurement process, allowing repeated measurements to be
performed with arbitrary high accuracy. 3) The authors suggest
that the ideas developed from quantum non-demolition measurements
can be applied for processing information-carrying light beams
using "noiseless" amplifying systems. The authors also suggest
that present and future quantum non-demolition measurement
research will range from improving the reliability of these
techniques through the use of new and more compact highly
nonlinear materials to solving technical problems such as
attaining single-photon resolution in the detection of small
photon numbers. "In the optical domain, to be able to watch
individual photons fly by will be the ultimate goal of any
quantum non-demolition measurement."
-----------
P. Grangier et al: Quantum non-demolition measurements in optics.
(Nature 10 Dec 98 396:537)
QY: Philippe Grangier [philippe.grangier@iota.u-psud.fr]
-----------
Text Notes:
... ... *Note #1: The difference AB - BA is called the
"commutator" of A and B, and the specification of this value is
known as a "commutation relation". The commutator of A and B is
sometimes denoted as [A,B]. In quantum mechanics, certain
dynamical variables (called "canonical conjugate variables" or
"complementary variables") satisfy the commutation relation
(AB - BA) = ih/2ã, where i is the square root of (-1) and
h is the Planck constant. In the Heisenberg uncertainty relation
(Uncertainty Principle; Indeterminancy Principle), the minimum
value of the product of the uncertainties in A and B is of the
order of magnitude of the Planck constant.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 19Feb99
-------------------
Related Background:
ON THE ORIGIN OF QUANTUM-MECHANICAL COMPLEMENTARITY
One of the most famous experiments in physics is the "two-slit"
experiment in which a beam of radiation simultaneously penetrates
two adjacent slits in a barrier with the formation of interfer-
ence patterns on the far side of the barrier, the interference
patterns produced by the wave character of the radiation entit-
ies. In physics, the *complementarity principle is the principle
that in nature any entity has two complementary aspects, particle
and wave, the two aspects related by momentum, energy, wave-freq-
uency, wavelength, and Planck's constant. In quantum theory, the
complementarity principle is manifested by wave-like behavior
(e.g., interference) occurring only when the different possible
paths that a particle can take are indistinguishable. A "which-
path" detector is any detector that determines the actual path
taken by a particle, the determination inevitably resulting in a
coupling of the particle to the measuring environment, which in
turn results in suppression of interference ("dephasing"). This
is usually explained in terms of Heisenberg's uncertainty
principle, which states the acquisition of spatial information
increases the uncertainty in the momentum of the particle, thus
destroying the interference. ... ... S. Duerr et al now report a
which-way experiment in an atom *interferometer in which the
"back action" of path detection on the momentum of the atom is
too small to explain the disappearance of the interference
pattern. Instead, the authors attribute the disappearance of the
interference pattern to correlations between the which-way
detector and the atomic motion, rather than to the uncertainty
principle. The authors suggest their results indicate that
complementarity is not enforced by the uncertainty relation.
-----------
S. Duerr et al (3 authors at the University of Konstanz, DE):
Origin of quantum-mechanical complementarity probed by a "which-
way" experiment in an atom interferometer.
(Nature 3 Sep 98 395:33)
QY: G. Rempe 
-----------
Text Notes:
... ... *complementarity principle: Niels Bohr (1885-1962) first
introduced his idea of complementarity in a lecture delivered at
a meeting on 16 September 1927 at Lake Como (IT). The idea has
gone through many refinements and restatements, and is now
usually presented in terms of wave-particle duality. Bohr's
original idea was that complementarity is more fundamental than
the uncertainty principle.
... ... *interferometer: In general, an interferometer is any
instrument that detects the interference patterns of light
(radiation) split into two or more beams that are subsequently
combined again.
-------------------
Summary & Notes by SCIENCE-WEEK  25Sep98
-------------------
Related Background:
DEPHASING IN ELECTRON INTERFERENCE BY A WHICH-PATH DETECTOR
... Fermions (electrons, protons, neutrons) are particles that
obey the Pauli exclusion principle: i.e., no two fermions of the
same kind can occupy the same quantum state. The interferometer
in this report was a microscale device with dimensions of a few
microns and involving a 2-dimensional electron gas.
... ... Buks et al (5 authors at Weizmann Institute of Science,
IL) report the dephasing effects of a which-path detector on
electrons traversing a double-path interferometer, and that
varying the sensitivity of the detector can affect the visibility
of the oscillatory interference signal, thereby verifying the
complementarity principle for fermions. This is apparently the
first study involving controllable dephasing via a which-path
detector. The authors suggest the technique may have other
applications to fundamental problems in quantum mechanics.
QY: M. Heiblum [heiblum@wis.weizmann.ac.il]
(Nature 26 Feb 98) (Science-Week 13 Mar 97)
-------------------
Related Background:
SQUEEZED LIGHT EXPERIMENTS REVEAL NON-CLASSICAL CORRELATIONS
In quantum physics, conjugate variables (also known as complem-
entary variables) are a pair of physical variables linked by the
Heisenberg Uncertainty Principle: one variable, but not both, can
be precisely specified at the same time. A "squeezed state", a
concept first introduced into radiation theory in the 1980s, is a
quantum state in which accurate specification of one variable of
a pair of conjugate variables increases the uncertainty of the
other variable. In the context of the physics of light, for
example, the uncertainty of the phase of light can be decreased
at the expense of increased fluctuations of amplitude. Zbigniew
Ficek and Peter Drummond (University of Queensland, AU), in a
review of nonclassical excitation in spectroscopy with squeezed
light, point out the modifications of the radiative properties of
atoms in the presence of squeezed light that have been predicted:
inhibition of the atomic decay process, squeezing-induced trans-
parency, population trapping, amplification without population
inversion, etc., and the authors suggest that nonclassical
(nonlinear) spectroscopy presents new physical effects not
obtained with conventional radiation sources.
QY: P. Drummond [drummond@physics.uq.edu.au]
(Physics Today September 1997) (Science-Week 17 Oct 97)


3. EIGHT CALVES CLONED FROM SOMATIC CELLS OF A SINGLE ADULT
The technique of nuclear transfer (nuclear transplantation),
which involves the transfer of a nucleus from one cell to another
cell whose nucleus has been previously removed, is an efficient
technique for assessing the developmental potential of a nucleus
and for analyzing the interactions between the donor nucleus and
the recipient cytoplasm. In amphibians, successful nuclear
transfer has been reported for the transfer of *blastula cells to
oocytes (egg cells), with successful development of cells into
tadpoles and juvenile frogs. Other cell types, including *germ
cells and somatic cells from tadpoles, have also been shown to
have developmental totipotency: their nuclei directed the
formation of fertile amphibians. However, despite extensive
studies in amphibians, progeny have not been generated from adult
cell nuclei. This obstacle was recently overcome in sheep and
mice, and nuclei from fetal *fibroblast cells have directed the
formation of lambs and calves. In 1998, nuclear transfer was
reported to have been successfully used to produce fertile mice
from *cumulus cells collected from *metaphase II oocytes.
... ... Y. Kato et al (8 authors at 3 installations, JP) now
report cloning of calves at a high rate using cumulus cells and
*oviductal epithelial cells that were *passaged several times in
vitro. The authors report that 8 calves were derived from
*differentiated cells of a single adult cow, 5 calves from
cumulus cells and 3 calves from oviductal cells, out of 10
embryos transferred to surrogate cows. All calves were visibly
normal, but 4 calves died at or soon after birth from
*environmental causes, and postmortem analysis revealed no
abnormality. The authors suggest these results demonstrate that
bovine cumulus and oviductal epithelial cells of the adult have
the genetic content to direct the development of newborn calves.
-----------
Y. Kato et al: Eight calves cloned from somatic cells of a single
adult.
(Science 11 Dec 98 282:2095)
QY: Yukio Tsunoda [tsunoda@nara.kindai.ac.jp]
-----------
Text Notes:
... ... *blastula cells: The blastula is an early embryonic stage
in which the embryo is a hollow fluid-filled ball of cells one
layer thick.
... ... *germ cells and somatic cells: Germ cells are the
reproductive cells, egg cells and sperm cells, while somatic
cells are all other cells.
... ... *fibroblast cells: A type of connective tissue cell,
secreting structural proteins (e.g., collagen) that form certain
tissue components, including the extracellular matrix.
... ... *cumulus cells: Cells surrounding the ovulated mammalian
egg cell, and which quickly disperse in the presence of sperm.
... ... *metaphase II: In general, meiosis is the process of
reductive cell division leading to progeny cells containing half
the genetic complement of the parent cell. In animals, meiosis
occurs twice (a first meiosis and a second meiosis), and
metaphase II is one of the early stages of the second meiosis.
... ... *oviductal epithelial cells: In animals, epithelial cells
(epithelium) compose the cell layers that form the interface
between a tissue and the external environment, for example, the
cells of the skin, the lining of the intestinal tract, and the
lung airway passages.
... ... *passaged: In this context, the term "passage" refers to
a replication of cells in culture. The phrase "passaged several
times" refers to serial replication.
... ... *differentiated cells: Refers to developmental cell
specialization (morphology and biochemistry) resulting from
activation (and/or deactivation) of specific parts of the cell
genome.
... ... *environmental causes: In this study, one calf died from
pneumonia following heat stroke, and 3 calves died from
congenital birth dysfunctions or traumas. The other 4 calves
remained healthy.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 19Feb99
-------------------
Related Background:
CLONED TRANSGENIC CALVES FROM FETAL FIBROBLASTS
Research has been in progress for more than a decade to develop a
system for genetic modification and large-scale cloning in
cattle, an important species in agriculture, biotechnology, and
human medicine. During the past 18 months, there has been much
publicity concerning the cloning of sheep using somatic cell
donor cells, the research conducted by the Wilmut group in the
UK. ... ... Now Cibelli et al (8 authors at 3 installations, US)
report similar results (but with a different method) in cattle.
Actively dividing fetal fibroblasts were genetically modified
with a marker gene, a clonal line was selected, and the cells
were fused to enucleated mature oocytes. Out of 28 embryos
transferred to 11 recipient cows, three healthy, identical,
transgenic calves were generated. Furthermore, the life span of
near senescent donor fibroblasts could be significantly extended
by nuclear transfer. With the ability to extend the life-span of
these primary cultured cells, this system would be useful for
inducing complex genetic modification in cattle. The authors
suggest their somatic cell nuclear transfer procedure could
improve the efficiency of producing transgenic cattle and broaden
the scope of applications for transgenic cattle.
QY: James M. Robl 
(Science 22 May 98 280:1256) (Science-Week 12 Jun 98)


4. ON DNA MICROSATELLITES
In general, "satellite DNA" is a type of DNA consisting mostly of
repeated sequences not transcribed into RNA. In an operational
sense, satellite DNA was originally any fraction of DNA that
differs sufficiently in its base composition from that of the
majority of the DNA fragments that separate into bands during
*cesium chloride gradient centrifugation. The satellite DNA
fraction produces a small "satellite" peak on the shoulder of the
main DNA distribution peak, and thus the terminology. Satellite
DNA is now defined as arrays of tandemly repeated sequences, in
some cases involving hundreds of nucleotide bases. In the human
genome, satellite DNA apparently comprises as much as 30 percent
of genomic DNA. "Minisatellite DNA" has been defined as arrays of
tandemly repeated sequences of at least 10 base pairs
interspersed with genomic DNA. "Microsatellite DNA" has been
defined as tandem arrays of mono-, di-, tri-, and
tetranucleotides interspersed with other genomic DNA. In
*eukaryotes, the long-repeat-sequence satellite DNA tends to be
localized near the *chromosome centromeres; minisatellite DNA
tends to be localized at chromosome ends; microsatellite DNA is
in general randomly dispersed in the genome. Satellite,
minisatellite, and microsatellite DNA have all been categorized
as part of the larger rubric of "junk DNA" -- apparently
functionless segments of DNA that are replicated along with the
rest of the genome. ... ... E.R. Moxon and C. Wills (2
installations, UK US) present a review of recent work on
microsatellite DNA, with a focus on the evidence that
microsatellite DNA may be of considerable importance for the
adaptation of organisms to changing environments. The authors
make the following points: 1) Of the approximately 3 billion
nucleotide bases in the human genome, only 10 to 15 percent
comprise genes. Some of the non-gene base sequences have apparent
control and structural functions, but most non-gene DNA has no
apparent purpose ("junk DNA"). 2) During the past several years,
there has been evidence that microsatellite DNA, at least in
bacteria, may be involved in a variety of important functions. In
certain disease-causing bacteria, for example, the microsatellite
DNA repeat sequences promote the emergence of new properties that
can enable the microbes to survive potentially lethal changes in
the environment. This role of microsatellite DNA in bacteria is
apparently dependent on the promotion of enormous evolutionary
diversity by the repeat sequences. The key is that the
microsatellite DNA repeats are especially prone to DNA-
replication errors, resulting in mutated genes that in turn
produce new proteins. In general, such diversity ensures that at
least one bacterium in a population can survive the immune system
of its host (or other defenses) and then can replicate to produce
a new and thriving colony. 3) In humans, the only function so far
assigned to microsatellite DNA is negative: microsatellite DNA
has been related to a variety of neurological diseases. There is
also evidence that microsatellite DNA sequences change in length
early in the development of some cancers, making the repeat
sequences useful markers for early cancer detection. Also in
humans, because the length of microsatellite DNA sequences may
vary from one individual to the next, they are used in the
identification procedure known as DNA profiling or DNA
"fingerprinting". 4) In general, what makes microsatellite DNA so
important for evolution is its extremely high mutation rate:
microsatellite DNA is 10^(4) times more likely to gain or lose a
repeat sequence from one generation to the next than an ordinary
gene is to undergo the single-base mutation that may produce a
disease. In addition, although it is quite rare for a single-base
mutation to mutate back again to its benign state, microsatellite
DNA repeat sequences can apparently readily return to their
former lengths, often within a few generations.
-----------
E.R. Moxon and C. Wills: DNA microsatellites: Agents of
Evolution?
(Scientific American January 1999)
QY: E. Richard Moxon, University of Oxford, UK
-----------
Text Notes:
... ... *cesium chloride gradient centrifugation: The salt cesium
chloride forms dense solutions in water, and so is used in
"isopycnic centrifugation" to separate DNA molecules of different
densities. Isopycnic centrifugation (band centrifugation) is a
separation technique in which macromolecules are subjected to a
centrifugal field in a solvent containing a density gradient. In
the solvent column, the macromolecules arrange themselves in
bands (isopycnic bands) where the density of the solvent is the
same as that of the particular macromolecule.
... ... *eukaryotes: Eukaryotes are cells (or organisms
consisting of such cells) with internal membrane-bound organelles
such as a nucleus.
... ... *chromosome centromeres: In cells with chromosomes, the
chromosomes are the physical structures into which DNA is
organized and on which genes are carried. The "centromere" is a
region of the chromosome to which traction fibers are attached
during replication.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 19Feb99


5. ELEVATING VITAMIN E CONTENT OF PLANTS VIA GENETIC ENGINEERING
The *chloroplasts of higher plants produce numerous compounds
important for human agriculture and nutrition. *Tocopherols, the
lipid-soluble *antioxidants sometimes known collectively as
vitamin E, are one such group of compounds and are synthesized
only by photosynthetic organisms. The 4 naturally occurring
tocopherols, alpha-, beta-, gamma-, and delta-tocopherol, differ
only in the number and position of methyl substituents on the
aromatic ring. In addition to their role as antioxidants,
tocopherols stabilize polyunsaturated fatty acids within *lipid
bilayers by protecting them from *lipoxygenase attack. Of
tocopherol species present in foods, alpha-tocopherol is the most
important to human health and has the highest vitamin E activity.
Although all tocopherols are absorbed equally during digestion,
only alpha-tocopherol is preferentially retained and distributed
throughout the body. Alpha-tocopherol is an essential component
of mammalian diets, and intakes in excess of the US recommended
daily allowances are apparently correlated with decreased
incidence of a number of degenerative human diseases. Plant oils,
the main dietary source of tocopherols, typically contain alpha-
tocopherol as a minor component, but with high levels of
biosynthetic precursor, gamma-tocopherol. ... ... D. Shintani and
D. DellaPenna now report the use of genetic engineering to clone
the final enzyme in alpha-tocopherol synthesis, gamma-tocopherol
methyltransferase. The authors report that *overexpression of
gamma-tocopherol methyltransferase in *Arabidopsis seeds shifted
oil composition in favor of alpha-tocopherol. The authors suggest
that similar increases in agricultural oil crops would increase
vitamin E levels in the average US diet.
-----------
D. Shintani and D. DellaPenna: Elevating the vitamin E content of
plants through metabolic engineering.
(Science 11 Dec 98 282:2098)
QY: Dean DellaPenna [della_d@med.unr.edu]
-----------
Text Notes:
... ... *chloroplasts: Chloroplasts are cell organelles involved
in photosynthesis, and are found in all photosynthetic plant
cells. The typical higher plant chloroplast is lens-shaped and
approximately 5 microns in diameter. The number per cell can vary
from 1 to over 100, depending on the organism. There is some
evidence that chloroplasts may have originated from
photosynthetic bacteria that became *endosymbiotic with plant
cells.
... ... *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.
... ... *Tocopherols: "Tocopherol" is a generic term for di- and
trimethyltocols. Alpha-tocopherol is 5,7,8-trimethyltocol.
Although the tocopherols are sometimes known collectively as
"vitamin E", the usual referent for vitamin E is alpha-
tocopherol.
... ... *antioxidants: In general, an antioxidant is any
substance that opposes oxidation or inhibits reactions produced
by dioxygen or peroxides. An antioxidant is usually effective
because it can itself be more easily oxidized than the substance
protected. The term is often applied to substances that can trap
free radicals, thereby breaking a chain reaction that normally
leads to extensive biological damage.
... ... *lipid bilayers: Lipid bilayers are spontaneously
forming self-organizing bimolecular layers of certain molecules
(lipids) with long nonpolar chains terminated by a polar group. 
Such molecules are found in cell membranes, and also in soaps. A
variety of artificial lipid bilayer membrane systems can be
investigated in the laboratory. The cell membrane itself is
basically a lipid-bilayer structure.
... ... *lipoxygenase: In general, any member of a group of
enzymes that catalyze the oxidation of polyunsaturated fatty
acids to a particular corresponding hydroperoxide. Such enzymes
are found widely distributed in plants and animals (including
humans).
... ... *overexpression: In general, the term "expression" refers
to any gene activity, but particularly to activity that results
in the production of the specific protein encoded by the gene.
The expression of genes is closely regulated in the cell, so that
underexpression and overexpression are potential pathological
abnormalities of cell function. In the context of this report,
however, overexpression is genetically engineered in a plant to
produce a result of potential human benefit.
... ... *Arabidopsis: (Arabidopsis thaliana) (thale cress) A weed
of the mustard family with a small genome of 120 million base
pairs. Arabidopsis is now an important laboratory species, and it
is presently the model for physiological, biochemical, cell
biological, and developmental studies of over 250,000 plant
species. 
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 19Feb99
-------------------
Related Background:
AGRICULTURAL GENOMICS PROPOSED AS 3RD TECHNOLOGICAL REVOLUTION
In an editorial in the journal Science, Philip H. Abelson
proposes that the next great revolution after the Industrial
Revolution and the computer-based revolution is already underway
and is the genomics revolution, and that the greatest ultimate
global impact of genomics will arise from the manipulation of the
DNA of plants. In the future, the world will obtain most of its
food, fuel, fiber, chemical feedstocks, and some of its
pharmaceuticals from genetically altered vegetation and trees.
Major companies such as Dow Chemical, DuPont, Monsanto, and
Novartis are spending billions of dollars annually on genetic
engineering and on acquiring stakes in genome-oriented companies.
Humans today employ the capabilities of relatively few plants.
Abelson suggests the major challenge is to explore the
opportunities inherent in the hundreds of thousands of plant
species.
QY: P.H. Abelson [science_editors@aaas.org]
(Science 27 Mar 98) (Science-Week 17 Apr 98)


6. A CELLULAR RECEPTOR FOR THREE DIFFERENT PATHOGENS
Pathogenic bacteria are adapted to exploit a variety of host cell
functions, and host cell receptors usually serve as the initial
target for bacterial interaction with a specified cell type.
Mycobacterium leprae, the causative organism of leprosy, is an
intracellular pathogen that invades *Schwann cells of the
*peripheral nervous system, causing damage to peripheral nerves,
and leaving patients with disabilities and deformities.
*Arenaviruses include several causative agents of fatal human
*hemorrhagic fevers, among these lymphocytic choriomeningitis
virus and Lassa fever virus. Alpha-dystroglycan, a *peripheral
cell membrane protein, is a component of the dystroglycan complex
(*dystrophin-*glycoprotein), a complex involved in early
development and morphogenesis and in the pathogenesis of muscular
dystrophies. Now two research groups report that the leprosy
bacterium and the two mentioned virus pathogens all apparently
interact with the same molecular receptor -- alpha-dystroglycan.
... ... A. Rambukkana et al (8 authors at 4 installations, US)
report that alpha-dystroglycan serves as a Schwann cell receptor
for M. leprae, the bacterium specifically binding to alpha-
dystroglycan when the protein is in solution or in its natural
state on the surface of cells. The binding apparently involves
the membrane protein *laminin-2, which together with alpha-
dystroglycan acts as a linkage between the *extracellular matrix
and the *cell cytoskeleton. The authors suggest that as part of
the infection process, M. leprae uses this linkage in its
interaction with Schwann cells.
... ... W. Cao et al (10 authors at 5 installations, US UK)
report the purification from cells of a peripheral membrane
protein interactive with several arenaviruses, including
lymphocytic choriomeningitis virus and Lassa fever virus, the
membrane protein identified as alpha-dystroglycan. The authors
also report that soluble alpha-dystroglycan blocked both
lymphocytic choriomeningitis virus and Lassa fever virus
infection of cultured mouse cells. Also, cells bearing a *null
mutation of the gene encoding dystroglycan were resistant to
lymphocytic choriomeningitis virus infection, and reconstitution
of dystroglycan expression in null mutant cells restored
susceptibility to such virus infection. The authors suggest their
results indicate that alpha-dystroglycan is a cellular receptor
for both lymphocytic choriomeningitis virus and Lassa fever
virus.
-----------
A. Rambukkana et al: Role of alpha-dystroglycan as a Schwann cell
receptor for Mycobacterium leprae.
(Science 11 Dec 98 282:2076)
QY: Anura Rambukkana [rambuka@rockvax.rockefeller.edu]
-----------
W. Cao et al: Identification of alpha-dystroglycan as a receptor
for lymphocytic choriomeningitis virus and Lassa fever virus.
(Science 11 Dec 98 282:2079)
QY: Michael B.A. Oldstone [mbaobo@scripps.edu]
-----------
Text Notes:
... ... *Schwann cells: Glial cells are "support" cells in the
central and peripheral nervous systems, acting as physical and
chemical buffers between neurons and their environment, and in
the peripheral nervous system, Schwann cells are a type of glial
cell responsible for producing the multiple membrane layers
called "myelin" that enfold nerve axons and make rapid
transmission of electrical signals possible.
... ... *peripheral nervous system: In general, this refers to
all nerve fibers and neurons that lie outside the brain and
spinal cord.
... ... *Arenaviruses: These are spherical viruses, 50-300
nanometers in diameter. The genome is 10-14 kilobases in size and
consists of 2 single-stranded RNA molecules. Some of these
viruses establish chronic infections in rodents, and humans are
infected by contact with rodent excreta.
... ... *hemorrhagic fevers: This is a generic term for a number
of different diseases caused by different viruses (one type of
which are the arenaviruses). Common elements are high fever,
organ bleeding, hypotension, shock, etc. Included in this group
of diseases are Lassa fever, Ebola fever, Marburg virus fever,
etc.
... ... *peripheral cell membrane protein: In this context, the
term "peripheral" refers to the exterior surface of the cell
membrane.
... ... *dystrophin: The gene product dystrophin is a protein of
molecular weight 427,000, and it appears to be completely absent
from patients affected by Duchenne muscular dystrophy, the most
common type of muscular dystrophy. The protein, whose function is
unclear, is apparently localized in the membranes of muscle
cells.
... ... *glycoprotein: Glycoprotein is a type of carbohydrate-
protein.
... ... *laminin-2: Laminin is a large glycoprotein that is known
to mediate the attachment, migration, and organization of cells
into tissues during embryonic development. Laminins of various
composition and amino acid sequences have been categorized as
laminins 1 to 5.
... ... *extracellular matrix: In general, the extracellular
matrix is a layer consisting mainly of proteins and
glycosaminoglycans that form a sheet underlying endothelial and
epithelial cells. The molecular constituents of the matrix are
secreted by cells in the vicinity. Endothelial cells are the
cells that line blood vessels; epithelial cells compose the cell
layers that form the interface between a tissue and the external
environment, for example, the cells of the skin, the lining of
the intestinal tract, and the lung airway passages.
... ... *cell cytoskeleton: The internal quasi-rigid matrix of a
cell, determining cell shape and involved in cell replication.
... ... *null mutation: In this context, a mutation resulting in
the absence of a protein.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 19Feb99


7. EARLY PHYSIOLOGICAL ABNORMALITIES IN SIV INFECTION
Simian immunodeficiency virus (SIV) is an analogue of human
immunodeficiency virus (HIV) that can infect various species of
monkeys. In HIV infection, central nervous system damage and
dysfunction are devastating consequences, involving
neuropsychological impairment, motor disorders, and dementia.
There is evidence that cells of *macrophage lineage in the
central nervous system are infected by HIV, and that macrophages
can be a major source of replicating virus in the later stages of
the disease, but at the present time, the events in the central
nervous system leading to neurological dysfunctions remain
unknown. What has been observed is that in HIV-infected
individuals multiple physiological parameters such as sleep
patterns, *psychomotor performance, and visual-, auditory-, and
somatosensory-*evoked potentials are altered. Because most anti-
HIV agents do not cross the *blood-brain barrier, the central
nervous system can remain a reservoir for the virus and be
uniquely susceptible to continued damage by the virus during
systemic drug therapies. ... ... T.F.W. Horn et al (5 authors at
Scripps Research Institute, US) now report the detection of early
physiological abnormalities in simian immunodeficiency virus-
infected monkeys (5 male rhesus animals). Acute SIV infection
provoked by viral inoculation caused a disruption of the
*circadian rhythm (as manifested by rises in body temperature) in
all 5 animals during the period 1-2 weeks post-inoculation. This
was accompanied by a reduction in daily motor activity to 50
percent of control levels. Animals remained hyperthermic at 1 and
2 months post-inoculation, and returned to pre-inoculation
temperatures at 3 months after viral inoculation. Analysis of
sensory-evoked responses 1 month post-inoculation revealed
distinct infection-induced changes in auditory-evoked potential
*peak latencies that persisted at 3 months after viral
inoculation. The authors suggest these early physiological
abnormalities may precede the development of observable cognitive
or motor deficiencies and may provide an assay to evaluate agents
to prevent or alleviate neuronal dysfunction.
-----------
T.F.W. Horn et al: Early physiological abnormalities after simian
immunodeficiency virus infection.
(Proc. Natl. Acad. Sci. US 8 Dec 98 95:15072)
QY: Howard S. Fox [hsfox@scripps.edu]
-----------
Text Notes:
... ... *macrophage: In the immune system, macrophages are
amoeba-like leukocytes (white blood cells) that are able to
surround and digest foreign entities such as bacteria and
protozoa.
... ... *psychomotor: In general, the term "psychomotor" refers
to a psychically (mentally) determined movement as opposed to a
movement produced by any other cause (e.g., a reflex).
... ... *evoked potentials: (evoked responses) The term "evoked
potential" refers to an electrophysiological measurement in which
a sensory signal (flash of light, tone, etc.) or cognitive signal
stimulates a response detected from the scalp or cerebral cortex,
the response presumably representing the response of the brain to
the stimulus. The evoked potential is reproduced as an averaged
trace with latency (time interval between stimulus onset and
response) and amplitude (height of response) within a series of
generated waveforms. The averaging process essentially pulls the
response out of the inherent physiological electrical "noise"
background produced by the ongoing activity of the brain. Evoked
potentials, under appropriate measurement circumstances, have
high replicability, and they can be clinically useful to detect
subclinical impairment of central sensory pathways.
... ... *blood-brain barrier: A selective mechanism opposing the
passage of most ions and large molecular-weight compounds from
the blood to brain tissue, the mechanism operating in a
continuous layer of endothelial cells connected by tight
junctions. "Endothelial cells" are flat cells forming a layer
lining blood vessels, lymphatic vessels, the heart, etc., and 
"tight junctions" are specialized junctions between cells that
essentially seal the cells together so that most molecules cannot
pass across a sheet of such cells.
... ... *circadian rhythm: Many organisms (including humans)
exhibit daily (circadian) rhythms, cyclical variations in various
bodily functions, metabolisms, etc., even in constant light or
constant darkness. In simple organisms, the pacemakers are
biochemical reaction loops; in higher organisms, complex
signaling structures are involved in the rhythms.  
... ... *peak latencies: In this context, the evoked potential
response latency, i.e., the time interval between stimulus onset
and evoked response.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 19Feb99
-------------------
Related Background:
ON NEW DEVELOPMENTS IN THE BIOLOGY AND TREATMENT OF HIV
HIV-1 is the subtype of HIV (human immune-deficiency virus) that
causes most cases of AIDS in the Western Hemisphere, Europe, and
Central, South, and East Africa. HIV is a retrovirus (subclass
lentivirus), and retroviruses are single-stranded RNA viruses
that have an enzyme called reverse transcriptase. With this
enzyme the viral RNA is used as a template to produce viral DNA
from cellular material. This DNA is then incorporated into the
host cell's genome, where it codes for the synthesis of viral
components. After initial transmission of HIV, viral particles
accumulate in blood to high levels within a few weeks, but levels
then fall as a result of the onset of the host immune response.
Thereafter, the disease usually remains quiescent for a prolonged
period, often for years or even decades, a phase termed "clinical
latency." ... ... F. Bushman et al present a short review of new
developments in HIV-1 biology and make the following points: 1)
Recent studies have revealed that the development of HIV viral
variants resistant to antiviral agents is a consequence of the
highly dynamic nature of the virus replication process. After
initial HIV infection, during the period of clinical latency, new
*virions are synthesized at a very high rate, with as many as
10^(10) virions produced and destroyed per day. The small HIV
genome of 10^(4) *base pairs is copied by two error-prone
enzymes: host-cellular *RNA polymerase and viral reverse
transcriptase. The enzyme reverse transcriptase makes
approximately 1 error per 10^(4) bases copied, so that each viral
genome bears on average one mutation. Because of this relatively
high mutation rate and the very large population of viruses in
vivo, many drug-insensitive mutant viruses are already present in
patients before treatment even begins. 2) The recent introduction
of effective anti-HIV drugs depends on the idea that if treatment
can suppress viral replication to a low enough level, then drug-
insensitive mutants have a greatly reduced probability of
arising. The development of anti-HIV *protease inhibitors has
brought this goal within reach for many patients. Most effective
of all therapies have been mixtures of antiviral drugs,
particularly "cocktails" of two reverse transcriptase inhibitors
and a protease inhibitor (triple combination therapy). 3)
Unfortunately, combination therapy is not a cure. Recent studies
report that patients who have maintained very low viral loads for
up to 30 months nevertheless harbor replication-competent virus
in a small number of *CD4(+) T-cells. This discovery of long-
lived reservoirs of virus-infected cells has caused hopes for a
cure to recede. 4) The emergence of drug-resistant variants of
HIV represents a long-term threat to the success of triple
combination therapy. It is estimated, for example, that 30 to 40
percent of HIV-infected people in the US may already have viruses
resistant to protease inhibitors. 6) Although many HIV-infected
people in the developed world can now be treated with therapy
likely to improve the length and quality of life, in the
developing world AIDS continues to spread and is unchecked. The
authors conclude: "The AIDS pandemic will likely remain
devastating for a long time to come." [*Note #1]
-----------
F. Bushman et al (3 installations, US)
New developments in the biology and treatment of HIV.
(Proc. Natl. Acad. Sci. US 15 Sep 98 95:11041)
QY: Frederic Bushman, Salk Institute, 10010 N. Torrey Pines Road,
La Jolla, CA 92037 US.
-----------
Text Notes:
... ... *virions: The complete virus particle that is
structurally intact and infectious.
... ... *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).
... ... *RNA polymerase: RNA polymerase is an enzyme that
polymerizes ribonucleoside triphosphates into RNA in the order
dictated by a DNA or RNA template. RNA polymerases are found in
all living cells, with one type found in prokaryotes (cells
without a cell nucleus and other membrane-bound organelles), and
3 types found in eukaryotes (cells with a cell nucleus).
... ... *protease: In general, any enzyme that cleaves proteins,
usually by hydrolysis. Late during HIV replication, the HIV virus
proteins must undergo precise cleavage at several sites to
complete formation of infectious virus particles. The HIV encodes
an enzyme that performs this function, and this enzyme is known
as the HIV protease.
... ... *CD4(+) T-cells: (CD4[+] lymphocytes) Lymphocytes (lymph
cells, lympholeukocytes) are a type of leukocyte (white blood
cell) responsible for the immune response. There are two classes
of lymphocytes: 1) the B-cells, when presented with a foreign
chemical entity (antigen), change into antibody producing plasma
cells; and, 2) the T-cells interact directly with foreign
invaders such as bacteria and viruses (cytotoxic T-cells), or
assist in the activation and cloning of antibody-producing B-
cells (helper T-cells). The T-cells express various surface
marker macromolecules, and CD4+ is the notation for a specific
expressed helper T-cell surface marker that can be identified by
assay. HIV exhibits great specificity for the helper T-cells of
the human immune system.
... ... *Note #1: A collection of back issue SW reports "HIV and
AIDS" can be found at [http://scienceweek.com/swfr027.htm].
An SW Focus Report explicating text "Viruses" can be found at
[http://scienceweek.com/swfr008.htm].
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 30Oct98
-------------------
Related Background:
APOPTOSIS OF NEURONS PRODUCED BY HIV-1 VIRUS
HIV-1 is the subtype of HIV (human immune-deficiency virus) that
causes most cases of AIDS in the Western Hemisphere, Europe, and
Central, South, and East Africa. HIV-1 has a complex genome that
encodes at least 6 accessory gene products that play a crucial
role in regulating viral replication. One of these products is
the 96-amino acid virus protein R (Vpr). This small accessory
protein is a multifunctional protein that is present in the serum
and cerebrospinal fluid of AIDS patients, and that apparently can
form cation-selective ion channels across in vitro planar lipid
bilayers. ... ... Pillar et al (4 authors at Australian National
University, AU) now report that the small HIV-1 accessory protein
(Vpr) associates with the plasma membrane of hippocampal neurons,
and causes a large inward cation current and depolarization of
the plasma membrane, and eventual cell death (apoptosis). The
authors suggest they have demonstrated a physiological action of
the virus protein and its mechanistic basis, and that these
findings may have important implications for neuropathologies in
AIDS patients who possess significant amounts of the virus
protein Vpr in cerebrospinal fluid.
QY: David A. Jans [David.Jans@anu.edu.au]
(Proc. Natl. Acad. Sci. US 14 Apr 98 95:4595)
(Science-Week 22 May 98)
-------------------
Related Background:
ANIMAL MODELS OF HIV-1 DISEASE
HIV-1 is the subtype of HIV (human immune deficiency virus) that
causes most cases of AIDS in the Western Hemisphere, Europe, and
Central, South, and East Africa. HIV is a retrovirus (subclass
lentivirus), and retroviruses are single-stranded RNA viruses
that have an enzyme called reverse transcriptase. With this
enzyme the viral RNA is used as a template to produce viral DNA
from cellular material. This DNA is then incorporated into the
host cell's genome, where it codes for the synthesis of viral
components. Immune system T-cells, particularly those bearing the
so-called CD4 surface protein marker, are the target cells for
HIV. J. McCune (Univ. of California San Francisco, US), in a
review of animal models of HIV-1 disease, distinguishes four
categories of such models: 1) mice bearing implanted and funct-
ional human tissue producing T-cells for in vivo studies; 2)
general transgenic mouse models for the analysis of specific
aspects of HIV-1 replication; 3) animal lentivirus models
(horses, sheep, goats, cattle, cats, nonhuman primates) for
analysis of the pathogenesis and transmission of lentiviral
agents; and 4) HIV infection models (rabbits and nonhuman
primates) for analysis of infections with HIV or infections with
subgenomic regions of HIV. The author suggests that no animal
model for HIV-1 disease satisfies all the preclinical needs, that
the search for alternatives continues, and that at the present
time "the best model for human disease is the human with the
disease." 
QY: Joseph M. McCune [mike_mccune.givi@quickmail.ucsf.edu]
(Science 19 Dec 97) (Science-Week 9 Jan 98)


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

NOTICES
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
SCIENCE-WEEK is delivered each week via Email and is available
only with a subscription fee of US$10 per year (52 issues). Email
delivery is guaranteed. For subscription information, contact:
[request@scienceweek.com]. A subscription information file is
also available at URL: [http://scienceweek.com/subinfo.htm].
Special group subscription rates are available.
FOCUS REPORTS: Selected reports are grouped in topical Focus
Reports available at the SCIENCE-WEEK website URL
[http://scienceweek.com].
CHANGE OF EMAIL ADDRESS: If you need to change the Email address
at which you receive SW, please send the information to
[request@scienceweek.com], and the change will be made and
confirmed the same day.
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-= 

The first issue of SCIENCE-WEEK appeared May 1, 1997, and it has
been published regularly each week since that date. We welcome
comments, suggestions, and criticisms from our subscribers.
Public letters relevant to any report are also welcome.
Editorial contact: [editors@scienceweek.com].

Editor/Publisher: Dan Agin
Managing Editor: Claire Haller
Associate Editor: Joan Oliner

Copyright (c) 1998 SCIENCE-WEEK/Spectrum Press Inc.
All Rights Reserved

---------------------------------------------
This publication is protected by U.S. and International Copyright
Laws, and no display, transmission, or duplication in any medium,
including BBS, Internet Email, website duplication, fax, or print
is permitted without the explicit consent of the holder of the
copyright. SCIENCE-WEEK is published by Spectrum Press Inc.,
3023 N. Clark St. #109, Chicago, 60657 IL, US.
---------------------------------------------