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ScienceWeek
SCIENCE-WEEK
A Weekly Digest of the News of Science
July 24, 1998
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We are the strangest species. We question everything,
measure the stars, sift the sand through our fingers,
gauge the bowels of the Earth. It is our destiny and
it will not stop.
-- Anonymous
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Contents of This Issue:
1. A Cheaper Chemistry Journal at US$2300 per Year
2. Gamma Ray Bursts: Tests of Quantum Gravity
3. Neptune's Eccentricity and the Nature of the Kuiper Belt
4. Seismology: Earthquakes and Nuclear Test Bans
5. First Synthesis of a Low-Mass Fullerene
6. Lipid Nanotubes and Helical Crystallization of Macromolecules
7. Gene Delivery and Liposome-DNA Complexes
8. On the Pathogenesis of HIV-1 Infection
9. An Expected Repertoire of Impotence Drugs
10. Archeology: Synthetic Basalt in Ancient Mesopotamia
Corrections
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1. A CHEAPER CHEMISTRY JOURNAL AT US$2300 PER YEAR
The US Association of Research Libraries is an affiliation of 81
libraries with a stated combined annual purchasing power of
approximately US$500 million. The association has a unit called
the Scholarly Publishing and Academic Resources Coalition
(SPARC), the ostensible purpose of the unit to seek ways and
agreements to reduce the cost of scientific journal subscriptions
to libraries. At the present time, the apparent modus operandi in
much of scientific journal publishing is to publish highly
specialized journals for a captive market (university and
corporate research libraries) and charge for these journals as
much as the market will bear. The publisher Elsevier, for
example, charges US$8000 per year for a subscription to its
weekly organic chemistry journal *Tetrahedron*, and US$5073 per
year for its journal *Neuroscience*. SPARC is now reported to
have an agreement from the American Chemical Society to publish a
new biweekly journal next year called *Organic Chemistry
Letters*, the subscription price to be US$2300 per year, with the
81 libraries of the association committed to subscriptions. This
proposed new chemical journal at US$2300 per year is now being
touted as a happy "solution" to the problem of journal prices. At
the indicated subscription price, the annual guaranteed revenue
to the American Chemical Society from this new journal will begin
at US$186,300 per year. Of course, the same revenue could be
generated from this new organic chemistry journal by providing it
online to 10,000 organic chemists worldwide at a subscription
price of less than US$20 per year, but then one loses the
commercial advantage of a solid captive market that will also
provide easily increased revenues in the future. The evident
focus is information concentrated via relatively few library
subscriptions rather than information widely disseminated via
personal subscriptions. Sooner or later, it seems, the libraries,
the scientific societies, and the scientific community in general
will need to decide unequivocally whether the purpose of the
publishing of scientific journals by scientific societies is to
disseminate the results of scientific research as widely as
possible or to generate revenues with commercial publishing as
the model.
(Chem. & Eng. News 6 Jul 98) (Science 3 Jul 98 281:21)
(Science-Week 24 Jul 98)
-------------------
Related Background:
RESEARCH LIBRARIES UNITING AGAINST JOURNAL PRICES
Several decades ago, a number of commercial publishers discovered
a paradigm for financial success: Found a new specialized
scientific journal, recruit an editorial board of specialists,
encourage high volume submission of papers with only cursory peer
review, inform research libraries they must carry the journal
because the specialty is important and because of the volume of
publications, and finally, over a period of years, gradually
increase the price of the journal several thousand per cent with
no fear of rejection by the captive library market. Other
publishers have used similar tactics in the publication of
scientific monographs and collections of papers: there are now on
the market a number of such books offered at a price of as much
as US$1 a page, the publisher's blurb more or less informing the
research library that without this item on your shelves your
library is not serious. The publishers say they cannot publish
research journals and monographs in the absence of maximum profit
to shareholders, and the research librarians say they can no
longer afford to maintain their libraries current in what is
being published. Scientific publishers are now giants of
industry, with the merger of Reed Elsevier and Wolters Kluwer
apparently about to produce a company with US$6 billion in
revenues publishing 1500 scientific and medical journals.
[Editor's note: The proposed merger fell apart.] For a time
it was hoped that electronic publishing of journals would
ameliorate the problem of library budgets, since the production
cost of electronic publication is only a small fraction of the
cost of print publication. But it seems the publishers are not
about to allow electronic publication to substantially reduce
their revenues: most journals now available separately in
electronic form do not charge much less for the electronic form
than they do for the printed form, and other journals may be
available in electronic form, but the electronic form is only an
adjunct to the printed form, and the electronic form is not
available as an independent publication. There may be a 90%
reduction in production cost for the electronic form, but there
is certainly not a 90% reduction in journal costs for the
research library. Now the libraries are apparently in revolt, and
a number of European libraries, particularly Dutch and German
libraries, are banding together to refuse electronic journal
subscription prices that are more than 80% of print subscription
prices. Alex Klugkist, chair of a consultative body of 15 Dutch
scientific libraries says, "We're fed up."
(Science 28 Nov 97) (Science-Week 19 Dec 97)
-------------------
Related Background:
CHEMIST CITES CRISIS IN DISTRIBUTION OF SCIENTIFIC INFORMATION
Alexandru T. Balaban, Professor of Organic Chemistry at the
University of Bucharest, argues that current methods of
distributing scientific information have caused critical
hardship to research workers in most countries of the world. In
Romania, for example, the only complete collection of *Chemical
Abstracts* exists in the capital city, Bucharest, although
universities and chemical research institutes are located in
five other cities. Balaban cites the paradox: Quality scientific
information is being produced, but only a tiny fraction of the
potential users can afford to buy and use this information. For
example, the Houben-Weyl *Methoden der organischen Chemie*,
important for any research in chemical synthesis, has more than
50 volumes with each volume priced at approximately $2000.
Recent volumes are practically unavailable, and many libraries
have stopped subscribing to the well-known Gmelin and Beilstein
series as well. Balaban concludes that a completely new approach
to the dissemination of scientific information is badly needed,
perhaps an approach utilizing the current interconnections
available via the Internet.
(American Scientist June 1997) (Science-Week 8 May 97)
2. GAMMA RAY BURSTS: TESTS OF QUANTUM GRAVITY
Quantum field theory is the mathematical fusion of quantum
mechanics with special relativity theory, and the term "quantum
gravity" refers to the fusion of quantum mechanics with general
relativity theory. The essential basis for these fusions is the
so-called "equivalence principle", which identifies the mass
involved in the gravitational force equation with the inertial
mass in the equation that relates any force to the product of
inertial mass and acceleration. (In general relativity, the
equivalence principle states that the observable local effects of
a gravitational field are indistinguishable from those arising
from acceleration of the frame of reference.) There are various
quantum field theories consistent with both quantum mechanics and
special relativity, all postulating that the gravitational force
between two quantum domain particles is generated by the exchange
of an intermediate particle (e.g., a graviton). But a quantum
gravity theory consistent with general relativity has not yet
been achieved, and there are physicists and mathematicians who
say the general form of such a satisfactory theory of quantum
gravity is not yet even clear -- that there is not yet even any
idea of what such a theory should look like.
... ... Amelino-Camelia et al (5 authors at 4 installations, UK
CH GR) suggest that the recent confirmation that at least some
*gamma ray bursts originate at cosmological distances indicates
that radiation from these bursts could be used to probe some of
the fundamental laws of physics, and that in particular, gamma
ray bursts will be sensitive to an energy dispersion predicted by
some approaches to quantum gravity. The essential idea is that
many of the bursts have structure on relatively rapid timescales,
which means that in principle it is possible to look for energy-
dependent dispersion of the radiation, as manifested in the
arrival times of the photons, if several different energy bands
are observed simultaneously. The authors suggest that a simple
estimate indicates that, because of their high energies and
distant origin, observations of these bursts should be sensitive
to a dispersion scale comparable to the Planck energy scale
(approximately 10^(19) *Gev), which is sufficient to test
theories of quantum gravity, and that such observations are
already possible using existing gamma ray detectors.
QY: G. Amelino-Camelia
(Nature 25 Jun 98 393:763) (Science-Week 24 Jul 98)
-------------------
Related Background:
... ... *gamma ray bursts: Gamma ray bursts are intense flashes
of *gamma rays detected at energies up to 10^(6) electronvolts.
They were discovered by US Air Force satellites in 1967 but not
declassified until 1973. The detection of these bursts averages
about 1 per day, and measurements indicate the distribution of
bursts is isotropic, i.e., they are uniformly distributed across
the sky. The current consensus is that gamma ray bursts are
produced by the merger of two *neutron stars, and up to this
point, the bursts that have been noted apparently originate
outside our own galaxy.
... ... *gamma rays: Gamma rays are radiation of high energy,
from about 10^(5) electronvolts to more than 10^(14)
electronvolts -- radiation with the shortest wavelengths and
highest frequencies, the gamma ray region of the electromagnetic
spectrum merging into the adjacent lower energy x-ray region.
... ... *neutron stars: Neutron stars are one of the possible
end-products of stellar evolution. If, following its terminal
stages, the remnant mass of a star is between 1.4 and 2 to 3
solar masses, the star will collapse into a neutron star, a body
with a radius of 10 to 15 kilometers, with a core so dense that
its component protons and electrons have merged into neutrons.
... ... *Gev: Also written as Bev, a billion electronvolts. The
quantity in the report is thus 10^(28) electronvolts. An
electronvolt is defined as the energy acquired by an electron
falling freely through a potential difference of one volt, and is
equal to 1.6022 x 10^(-19) joule.
3. NEPTUNE'S ECCENTRICITY AND THE NATURE OF THE KUIPER BELT
In 1951 the astronomer Gerard P. Kuiper (1905-1973) postulated
the existence of a belt of objects beyond the orbit of Pluto.
Both the existence and nature of the objects were matters of
speculation for decades, and finally in 1992 Jewitt and Luu
identified the first Kuiper object. The current estimate is that
as many as 10^(8) objects larger than 10 kilometers in diameter
may exist in what is called the "Kuiper belt", a disc that hugs
the plane of the planetary system and lies between 35 and 1000
*AU from the Sun. Observations to date have yielded some 55
trans-Neptune bodies with radii on the order of 100 km or larger,
and Pluto is considered by some astronomers to be a member of
this population. ... ... Now Ward and Hahn (2 installations, US)
present calculations that indicate that the small *orbital
eccentricity of Neptune may be a direct consequence of *resonant
wave interaction between Neptune and the Kuiper belt. The Kuiper
belt is subject to resonant perturbations from Neptune, so that
the transport of angular momentum density waves can result in
orbital evolution of Neptune as well as changes in the structure
of the Kuiper belt. The calculations indicate Neptune's
eccentricity could damp to its current value over the age of the
solar system if the Kuiper belt contains slightly more than an
Earth mass of material out to about 75 AU.
QY: William R. Ward, Southwest Research Institute, 1050 Walnut
Street, Suite 429, Boulder, CO 80302 US.
(Science 26 Jun 98 280:2104) (Science-Week 24 Jul 98)
-------------------
Related Background:
... ... *AU: Astronomical Unit. 1 AU = the mean distance from the
Sun to the Earth = approximately 93 million miles, and exactly
149,597,870 kilometers.
... ... *orbital eccentricity: This is a measure of the extent to
which an elliptical orbit departs from circularity. For a
circular orbit, eccentricity = 0. Neptune's eccentricity is quite
low (0.009) compared with the other planets in the solar system
(Earth's eccentricity = 0.017), although the eccentricities of
the planets do vary over long time-frames.
... ... *resonant wave interaction: In general, resonance is a
marked increase in the oscillation amplitude of a system when the
system is subjected to an oscillating force whose frequency is
the same or close to the natural frequency of the system as
determined by the system parameters. The waves mentioned in this
report are waves excited at resonance sites, locations where a
forcing frequency matches some natural frequency of the Kuiper
belt.
... ... In August 1989, the Voyager 2 spacecraft passed only 4400
kilometers above the cloud tops of Neptune and revealed the
first
details of the planet, its rings, and its satellites. Neptune has
an apparent rocky core, an inner mantle of liquid water,
methane,
and ammonia, and an outer shell of hydrogen and helium. The
intense atmospheric activity on Neptune is apparently driven by
heat flow from the interior, but the cloud top temperature is
-216 degrees centigrade. The diameter of the planet is
approximately 4 times the diameter of Earth, and its average
distance from the sun is approximately 30 AU.
-------------------
Related Background:
EVIDENCE FOR KUIPER BELT ORIGIN OF PLUTO AND TRITON
... ... Robert H. Brown and his associates (University of
Arizona, NASA Ames Research Center, California Institute of
Technology) have succeeded in obtaining spectroscopic
information from Kuiper Object 1993SC, which is apparently 300
kilometers in diameter. Using the spectra to determine the
surface composition of the object, and comparing the data to
that already obtained from Pluto and Neptune's moon Triton, the
result is consistent with the idea that Pluto, Triton, and the
Kuiper Belt objects may have a common solar system history, with
Pluto and Triton being the largest members of the population of
bodies that made up the early Kuiper belt.
(Science 9 May 97) (Science-Week 15 May 97)
4. SEISMOLOGY: EARTHQUAKES AND NUCLEAR TEST BANS
US seismologists and some US politicians are evidently in a
dispute concerning the effectiveness of the international nuclear
device explosion detection system. The disagreement specifically
concerns the report by India of nuclear device explosions in
India on this past May 11th and May 13th. Eliot Marshall, in a
review of the dispute, makes the following points: 1) The web of
sensors that encircles the globe, programmed to monitor
compliance with the Comprehensive Test Ban Treaty, detected the
May 11th explosion but did not detect the May 13th explosion. 2)
Politicians who oppose the treaty are arguing that since
monitoring is ineffective, the treaty is useless and money
appropriated for the detection system wasted. 3) However, a
consensus has emerged among seismologists that the system in fact
worked well, and that the May 13th nuclear device explosion
reported by India either did not occur or was of too low yield to
be detectable by the present system. India reported a blast of
800 tons, and most seismologists evidently believe a blast of 100
to 200 tons would have been detected by the system that is place.
4) The international detection system, which is managed by the
United Nations, involves 35 primary seismic monitoring stations
supported by 58 auxiliary stations that can be queried for data
as needed. Plans are underway for considerable expansion of this
detection system. Marshall concludes: "The only way to resolve
the debate about blast yields may be through independent studies
of the bomb test sites. These might provide a clear indication of
just how well the seismic watchdog performed. But at the moment,
neither India nor Pakistan is ready to invite such inspections."
QY: Eliot Marshall
(Science 26 Jun 98 280:2039) (Science-Week 24 Jul 98)
-------------------
Related Background:
A CONFLICT BETWEEN SEISMOLOGISTS AND DEFENSE ANALYSTS
It is an old adage that politics uses science, but a regrettably
frequent and insidious aspect of that use is the distortion of
science for political ends. On August 16, 1997 a geological event
occurred approximately 130 kilometers off the coast of Novaya
Zemlya. That Arctic island has been a Russian test site for
nuclear weapons, and politicians opposed to ratification of what
is called the Comprehensive Test Ban Treaty with the Russians are
claiming that geological event was a nuclear explosion and thus
evidence that the Russians are cheating. A press report suggest-
ing the geological event had "explosive characteristics" was
"leaked" from the U.S. Department of Defense to the Washington
Times, a conservative newspaper. But apparently most seismolog-
ists consider the geological event a seismic event -- in other
words, an earthquake -- and they are quite upset over the
distorted interpretation of the scientific evidence by the U.S.
Government. Whereas explosions produce predominantly compression
waves, earthquakes have a significant shear wave component, and
the August event apparently has the clear signature of an
earthquake. Greg van der Vink of the Incorporated Research
Institutions for Seismology, a collaboration of 90 universities
supported by the U.S. National Science Foundation to operate
seismology research facilities, says, "I don't know of any
seismologist who does not think that this was an earthquake."
Evidently Jesse Helms, Chairman of the U.S. Foreign Relations
Committee, disagrees. And evidently many seismologists are afraid
to be more vociferous because their research funding originates
with the U.S. Department of Defense.
(Nature 2 Oct 97) (Science-Week 17 Oct 97)
5. FIRST SYNTHESIS OF A LOW-MASS FULLERENE
Under appropriate non-equilibrium growth conditions, carbon atoms
form relatively stable hollow clusters of well-defined mass
number, collectively known as "fullerenes". The mass production,
purification, and condensation of such clusters into a molecular
solid is generally essential to full experimental characteriz-
ation. The initial discovery of C(sub60) in 1985, for example,
had to await a bulk synthesis method 6 years later before
detailed characterization of the molecule was possible. Gas-phase
experiments have indicated the existence of a wide range of
possible fullerene clusters, but beyond C(sub60) only a few pure
fullerene solids have been obtained, most notably C(sub70). Low-
mass fullerenes are of particular interest because their high
curvature and increased strain energy owing to adjacent
pentagonal rings could lead to solids with unusual intermolecular
bonding and electronic properties. ... ... Piskoti et al (3
authors at 3 installations, US) now report the synthesis of the
solid form of C(sub36) by the *arc-discharge method. They report
the development of purification methods that separate C(sub36)
from amorphous carbon and other fullerenes to yield saturated
solutions, thin films, and polycrystalline powders of the pure
solid form. The authors report observation of large increases in
the electrical conductivity of the solid on doping with alkali
metals, and they suggest that if C(sub36) could be made
sufficiently conducting -- either by doping or by structural
rearrangement (e.g., induced by pressure) -- one might expect
high-temperature superconductivity to be manifested.
QY: A. Zettl
(Nature 25 Jun 98 393:771) (Science-Week 24 Jul 98)
-------------------
Related Background:
... ... *arc-discharge method: In the present instance, the
method involves an originally designed helium-environment arc-
discharge chamber, with an arc between two 0.25 inch-diameter
graphite electrodes, using a DC current of 100 amperes while
maintaining a 1 millimeter gap between the electrodes. Arcing is
maintained for several minutes, until a uniform carbon film of
approximately 10 microns thickness coats a removable metal
substrate 10 centimeters from the discharge region.
-------------------
Related Background:
NEW EVIDENCE OF REACTIVITY OF FULLERENE SEGMENTS
Fullerenes are large molecules composed entirely of carbon, with
the chemical formula C(n), where n is any even number from 32 to
over 100. They apparently have the structure of a hollow spher-
oidal cage with a surface network of carbon atoms connected in
hexagonal and pentagonal rings. The present consensus is that the
reactivity of fullerenes is largely a result of the strain
associated with curving an aromatic network. Bronstein and Scott
now report that 26-carbon polycyclic aromatic hydrocarbon frag-
ments of fullerenes exhibit reactivity similar to a complete 60-
carbon fullerene, and the authors suggest the reactivity of
fullerenes can therefore be extended to curved (e.g., bowl-
shaped) but not necessarily closed molecules. They found the
reactive carbon in the bowl-shaped fragments to be the interior
carbon shared by three rings (as in complete fullerenes), while
in ordinary flat polycyclic aromatic hydrocarbons reactivity is
apparently located around the edges of the molecules. The results
were reported at the recent Chemical Congress of North America
(Cancun, MX).
QY: Hindy E. Bronstein, Boston College, 617-552-3100.
(Chem. & Eng. News 1 Dec 97) (Science-Week 12 Dec 97)
6. LIPID NANOTUBES AND HELICAL CRYSTALLIZATION OF MACROMOLECULES
A general approach for crystallization of proteins in a fast and
simple manner would be of great interest to biologists studying
protein structure-function relationships. ... ... Wilson-Kubalek
et al (4 authors at 2 installations, US) report a method for
promoting the formation of helical arrays of proteins in
conjunction with macromolecular assemblies. Electron micrographs
of the arrays are suitable for helical image analysis and 3-
dimensional reconstruction. The authors report that hydrated
mixtures of the glycolipid galactosylceramide and derivatized
lipids or charged lipids form *single-layer nanotubules. These
tubules bind proteins in a specific manner via high affinity
ligands on the polar head groups of the lipid or via
electrostatic interactions. Doping the galactosylceramide with a
nickel-containing lipid enabled the formation of helical arrays
of two histidine-tagged proteins. Doping with a *biotinylated
lipid allowed the crystallization of *streptavidin. Three
proteins with affinity for positively or negatively charged lipid
layers formed helical arrays on appropriately charged tubules.
The authors suggest the generality of their method may allow a
wide variety of proteins to be crystallized on lipid nanotubes
under physiological conditions.
QY: Ronald A. Milligan
(Proc. Natl. Acad. Sci. US 7 Jul 98 95:8040)
(Science-Week 24 Jul 98)
-------------------
Related Background:
... ... *single-layer nanotubules: The classical name for such
nanoscale lipid structures is single-layer tubular "micelles".
The lipid nanotubules in this study have an inner diameter of 160
angstroms and an outer diameter of 270 angstroms.
... ... *biotinylated: This refers to tagging with biotin. Biotin
(coenzyme R, vitamin H) is cis-hexahydro-2-oxo-1H-thieno[3,4,-
d]-
imidazoline-4-valeric acid. It is the D-isomer component of the
vitamin B2 complex, and is a small molecule with a high affinity
for the glycoprotein *avidin.
... ... *avidin and streptavidin: Avidin is a glycoprotein
obtained from egg white with a high affinity for biotin. A number
of reaction amplification and visualization methods involve
labelled avidin binding to macromolecules tagged with biotin.
Streptavidin is a type of avidin.
7. GENE DELIVERY AND LIPOSOME-DNA COMPLEXES
Complexes consisting of DNA mixed with oppositely charged
cationic *liposomes mimic natural viruses in their ability to act
as synthetic carriers of extracellular DNA across outer cell
membranes and nuclear membranes for *gene delivery. The use of
nonviral rather than viral methods for gene delivery has several
advantages, including avoidance of host immune responses and the
potential for transferring comparatively large pieces of
subsequently expressed DNA into cells (transfection). Partial
sections of first generation human artificial chromosomes on the
order of 1 million base pairs have been transferred into cells by
means of cationic liposomes, but only extremely inefficiently.
Insights into the transfection-related mechanisms at the
molecular and self-assembled levels may improve nonviral delivery
methods. ... ... Koltover et al (4 authors at (University of
California Santa Barbara, US) now report that in a lipid
composition regime used to transfect mammalian cells in culture,
a 2-dimensional columnar phase of mixtures of DNA complexed with
cationic liposomes is more efficient at transfection than a
lamellar structure. The efficient structure, derived from
synchrotron x-ray diffraction analysis, consists of DNA coated by
cationic lipid monolayers and arranged on a 2-dimensional
hexagonal lattice. Optical microscopy revealed that the lamellar
complex binds stably to anionic vesicles (models of cellular
membranes), whereas the more transfective columnar complexes are
unstable and rapidly fuse and release DNA upon adhering to the
anionic vesicles.
QY: Cyrus R. Safinya, Univ. of Calif. Santa Barbara 805-893-8000.
(Science 3 Jul 98) (Science-Week 24 Jul 98)
-------------------
Related Background:
... ... *liposomes: Liposomes are vesicles (spherules) in which
the lipid molecules are spontaneously arranged into bilayers with
hydrophilic groups exposed to water molecules both outside the
vesicle and in the core.
... ... *gene delivery: This is a general term for the
introduction of new genetic elements into the genomes of living
cells. The delivery problem is essentially conditioned by the
fact that the new genetic elements are usually large, and by the
presence of the outer cell membrane and the nuclear membrane
acting as barriers to incorporation of the new DNA into the
genome already present in the nucleus. Viruses possess various
natural biochemical methods for achieving gene delivery;
artificial gene delivery is one of the essential problems of
"genetic engineering". The most important barrier is apparently
the outer cell membrane, which is essentially a lipid barrier,
and introduction of any large complex into the cell requires a
fusion of one kind or another with this membrane. Liposomes,
which consist of lipid membranes themselves, and which can fuse
with outer cell membranes, are thus potential vehicles for
delivery of many substances, including DNA.
-------------------
Related Background:
ON RECEPTOR ACTIVATED RETROVIRAL MEMBRANE ASSOCIATION
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 into the host cell's
genome, where it codes for the synthesis of viral components.
Envelope proteins are the proteins found in the envelopes of
viruses in their virion stage (i.e., the entire virus as it
exists before or after the replication phase). Liposomes are
laboratory created vesicles (spherules) in which the lipid
molecules are spontaneously arranged into bilayers with
hydrophilic groups exposed to water molecules both outside the
vesicle and in the core. Rous sarcoma virus is a cancer-producing
virus that infects birds, discovered by Francis Peyton Rous
(1879-1970) in 1911, and the first discovered tumor-producing
virus. In 1966, Rous shared the Nobel Prize in Medicine and
Physiology for this work. Current models of the entry of
retroviruses into host cells propose conformational changes in
the envelope protein of the virus as a precursor to fusion of the
virus with the host cell membrane. ... ... Damico et al (3
authors at University of Pennsylvania, US) report the use of a
cell-free liposome-binding assay to study the behavior of a model
virus envelope protein (from Rous sarcoma virus). In the presence
of purified viral receptor, the viral envelope protein apparently
converts from a water-soluble form to a liposome membrane-
associated form, which is consistent with the conversion of the
envelope protein to its fusogenic state (the state involving
fusion with the host cell membrane). The authors suggest their
results provide direct evidence that receptor binding triggers
conversion of the virus envelope protein to a membrane-fusing
form, and illustrates that Rous sarcoma virus is a useful model
for the study of retroviral entry.
QY: Paul Bates
(Proc. Natl. Acad. Sci. US 3 Mar 98)
(Science-Week 10 Apr 98)
8. ON THE PATHOGENESIS OF HIV-1 INFECTION
Kahn and Walker (2 installations, US) review the pathogenesis,
clinical manifestations, diagnosis, and treatment of acute *HIV-1
infection. More than 30 million persons are estimated to be
infected with HIV-1 worldwide. In the US, more than 44,000 new
cases of infection will occur in 1998, and globally there are an
estimated 16,000 new cases daily. *Acute human immunodeficiency
virus type 1 (HIV-1) infection is a transient *symptomatic
illness associated with *high-titer HIV-1 replication and a
robust and expansive immunologic response to the invading
pathogen. From 40 to 90 percent of new HIV-1 infections are
associated with acute symptomatic illness within days to weeks
after initial exposure, with prevalent symptoms such as fever,
fatigue, rash, headache, and nausea. Studies with rhesus monkeys
with acute intravaginal simian immunodeficiency virus infection
have provided important insights into the sequence of cellular
events occurring in the earliest stages of infection, and the
authors make the following points concerning the pathogenesis of
HIV-1: 1) The most common mode of HIV-1 infection is sexual
transmission at the genital *mucosa, with an apparent initial
target of tissue *dendritic cells. Infected cells of the genital
mucosa then fuse with *CD4+ lymphocytes and spread to the deeper
tissues. 2) Within 2 days after infection, the virus can be
detected in *lymph nodes associated with the genital region.
Shortly thereafter, systemic dissemination occurs, and HIV-1 can
be cultured from plasma 5 days after infection (4 to 11 days in
humans). 3) Breaks in the mucosal barrier and increased
inflammation due to the presence of genital ulcer disease,
*urethritis, etc., increase the risk of acquiring HIV-1
infection. 4) Although infection is transmitted most frequently
across the genital mucosa, numerous reports demonstrate that in
humans infection can also be transmitted across the oral mucosa
as a result of genital-oral sex. Nasopharyngeal tonsil and
adenoid tissues are rich in cells of dendritic origin, which are
probably the initial target cells, facilitating the transmission
of the virus to CD4+ cells.
QY: Bruce D. Walker, Harvard Univ. Medical School 617-432-1550.
(New England J. Med. 2 Jul 98 339:33) (Science-Week 24 Jul 98)
-------------------
Related Background:
... ... *HIV-1: 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.
... ... *Acute human immunodeficiency virus type 1 (HIV-1)
infection: This should be distinguished from AIDS. Acquired
immunodeficiency syndrome (AIDS) is a secondary immunodeficiency
syndrome resulting from HIV infection and characterized by
opportunistic infections, malignancies, neurologic dysfunction,
and a variety of other syndromes.
... ... *symptomatic: With recognizable symptoms.
... ... *high-titer: High-density, as revealed by an assay
method.
... ... *mucosa: Refers to the mucous tissue lining various
tubular structures in the body.
... ... *dendritic cells: These are mononuclear cells with long
cytoplasmic processes. They function as antigen-trapping and
antigen-presenting cells. (antigen: a substance foreign to the
vertebrate host and capable of eliciting an immune response). The
shape of dendritic cells is "tree-like", hence their name. They
should not be confused with nerve cells, many of which also have
a "tree-like" shape, with processes called "dendrites".
... ... *CD4+ lymphocytes: Lymphocytes (lymph cells, lympho-
leukocytes) 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. The T-cells express
various surface marker macromolecules, and CD4+ is the notation
for a specific expressed T-cell surface marker that can be
identified by assay.
... ... *lymph nodes: The lymphatic system is a complex network
for the distribution of lymph fluid (which is similar to blood
plasma -- blood without red cells). Lymph is collected by
drainage from the tissues throughout the body, flows in the
lymphatic vessels through the lymph nodes, and is eventually
added to the venous blood circulation. Lymph consists of a clear
liquid portion, varying numbers of white blood cells (chiefly
lymphocytes), and a few red blood cells. The lymph nodes are
small bodies located throughout the lymph system and varying in
diameter from 0.1 to 2.5 centimeters.
... ... *urethritis: Any inflammation of the urethra.
9. AN EXPECTED REPERTOIRE OF IMPOTENCE DRUGS
According to the US National Institutes of Health, 20 to 30
million men in the US suffer from some form of penile erectile
dysfunction, and these numbers are apparently confirmed by the
phenomenal commercial success of Viagra, the brand name for the
drug sildenafil citrate. At the annual meeting of the American
Urological Association in San Diego (US) early in June, the drug
apparently dominated discussions. Elizabeth K. Wilson reviews
these discussions and makes the following points: 1) Viagra is
the first oral medication approved in the US for penile erectile
dysfunction, but other treatments working by different modes of
action are evidently on the way. 2) A variety of compounds have
been used to treat impotence: papaverine, prostaglandin E1,
sildenafil, phentolamine, apomorphine. And several other
compounds have been investigated as impotence remedies: L-
arginine, colforsin, trazodone. 3) The intracellular messenger
molecule cyclic guanosine monophosphate (cGMP) apparently plays a
key role in producing the physiological changes that lead to an
erection. 4) The process begins when *nitric oxide, released by
nerve cells or endothelial cells, diffuses into smooth muscle
cells in the walls of penile arteries and penile spongy erectile
tissue. 5) Nitric oxide binds to the heme component of the enzyme
guanylate cyclase, stimulating that enzyme to synthesize cGMP
from guanosine triphosphate. Increased levels of cGMP lead to
decreased calcium ion concentrations in the muscle cells, causing
the muscles to relax and blood to flow into the penis. The
concentration of cGMP is regulated by the activity of a second
enzyme, phosphodiesterase-5, which hydrolyzes cGMP to GMP
(guanosine monophosphate). 6) The consensus at the urology
meeting was apparently that within the next few years there will
appear a new generation of Viagra-like drugs, and that during
this time attention will also turn to biochemical remedies for
sexual dysfunction in women.
QY: Elizabeth K. Wilson
(Chem. & Eng. News 29 Jun 98) (Science-Week 24 Jul 98)
-------------------
Related Background:
... ... *nitric oxide: The gas nitric oxide is the prime member
of an entirely new class of neurotransmitters discovered only in
the 1990s. In the brain, the enzyme that synthesizes nitric oxide
(nitric oxide synthase) is localized in discrete populations of
neurons. In the peripheral autonomic nervous system, the enzyme
occurs in neurons that regulate the adrenal medulla, the
posterior pituitary, and the smooth muscle cells of the intestine
involved in *peristalsis. In all of these systems, nitric oxide
acts as a neurotransmitter released as a consequence of neural
activity. Nitric oxide has also been implicated as a messenger in
the response of macrophages (immune system cells) to cancer cells
and invading bacteria. It is also released from *endothelium in
response to acetylcholine and other vasodilators, with a
resultant relaxation of blood vessels. And, as noted in the
report, it is involved in penile erection. Nitric oxide is a free
radical with a half-life of only a few seconds, and its
concentration in tissues is difficult to establish
quantitatively. It should not be confused with nitrous oxide
("laughing gas"), which is an analgesic gas used as an auxiliary
in anesthesia in dentistry and surgery.
... ... *peristalsis: This refers to the regulated waves of
alternating contraction and relaxation of the intestine that move
its contents onward.
... ... *endothelium: A layer of flat cells lining blood vessels,
lymphatic vessels, the heart, etc.
10. ARCHEOLOGY: SYNTHETIC BASALT IN ANCIENT MESOPOTAMIA
The ancient inhabitants of Mesopotamia lacked raw materials such
as stone, metal ores, or large timber, but they did possess
alluvial silt in abundance, and they used this for pottery,
architecture, writing materials, objects of art, and tools such
as sickles. Now Stone et al (5 authors at 4 installations, US)
report that slabs and fragments of gray-black vesicular "rock"
superficially resembling natural *basalt but distinctive in
chemistry and mineralogy have been excavated at the 2nd
millennium BC Mesopotamian city of Mashkan-shapir, about 80
kilometers south of Baghdad (IQ). Most of the material appears to
have been deliberately manufactured by the melting and slow
cooling of local *alluvial silt. The high temperatures
(approximately 1200 degrees centigrade) required and the large
volume of material processed indicate an industry in which lithic
(i.e., pertaining to stone) materials were manufactured for
grinding grain and construction. The authors suggest that for
synthetic basalt to be produced required: 1) that the possibility
of melting soil had to have been conceived; 2) that the typically
small metal-smelting furnaces be increased in size without
decreasing the maximum temperatures attained; and 3) that the
resulting product be cooled relatively slowly to ensure adequate
crystal growth. The authors conclude: "This technology can only
have come about through experimentation and as part of the wider
process of innovation."
QY: E.C. Stone
(Science 26 Jun 98 280:2091) (Science-Week 24 Jul 98)
-------------------
Related Background:
... ... *basalt: Basalt is a dark gray to black *igneous rock of
volcanic origin that cools rapidly. It is found as basement
rock on land, and on sea floor spreading from mid-ocean ridges.
... ... *alluvial: Deposited by running water (e.g., silt).
... ... *igneous: Igneous rocks are rocks that have congealed
from a molten mass.
---------------------------------------------
CORRECTIONS:
In SW issue of 17 July 1998:
----------------------------
In Report #2:
"significant gravitational break on expansion"
should read:
"significant gravitational brake on expansion"
In Report #3:
"the time period 10^(-35) to 10^(-32) were quickly amplified"
should read:
"the time period 10^(-35) to 10^(-32) seconds after time zero
were quickly amplified"
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