ScienceWeek

SCIENCE-WEEK - Part 1/3

A Free Weekly Digest of the News of Science

March 20, 1998

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We measure things. We spend countless dull hours measuring the
swing of a pendulum, the heat of an acid, the twitch of a muscle.
But only with these measurements in hand can we begin our
dialogue with the Cosmos.
-- The Editors
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Contents of This Issue:

Part 1.
1. On Intellectual Property and the American University
2. Xenotransplantation: A Group of Letters
3. Near-Closure of a University Chemist Plagiarism Case
4. Women Now Substantial Portion of All New US Chemists
5. A Global Approximation Technique for Multivariate Systems

Part 2.
6. On Black Holes as Real Astronomical Objects
7. On the Geological Evolution of Venus
8. On Quantum Theory Without Observers
9. Subsurface Charge Accumulation in a Quantum Hall Liquid
10. A New Technique for Size Separation of Macromolecules
11. Hydrogen Hypothesis for the First Eukaryote
12. Polyketide Synthases as Modular Enzymes
13. A Model for the Mechanism of a Human Topoisomerase

Part 3.
14. Host Derived Amino Acids Support Symbiotic Bacteria
15. Identification of a Cell Membrane Nucleic Acid Channel
16. Plant Performance and Induced Responses to Herbivory
17. Single Neuron Control of Synaptic Efficacy
18. Characterization of an In Vitro Blood-Brain Barrier
19. Muscle Regeneration by Bone-Marrow-Derived Cells
20. Genetic Traces of Ancient Demography

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1. ON INTELLECTUAL PROPERTY AND THE AMERICAN UNIVERSITY
The Bayh-Dole Act (Public Law 96-517), first implemented in 1980,
has caused a profound change during the past 17 years in the
scientific enterprise of American universities. The primary
intent of the law was to foster the growth of technologically-
based small businesses by allowing them to own the patents that
arose out of federally sponsored research, with universities and
other nonprofit recipients of federal funding included in the
definition of small entities. Under the law the universities
would not develop patented technologies, but would license the
patents to industry, retaining royalties from such licenses, a
fraction of university royalties delivered as personal income to
inventors, the remainder of university royalties used for general
research and educational purposes. One result of all of this has
been that many major academic research installations in the US
now have as income from patent royalties revenues as great as the
total revenues of middle-size corporations -- in the range US$50
million to $100 million per year per university. ... ... In an
essay, L. Nelsen (Massachusetts Institute of Technology, US)
reviews this sea-change in the practicalities of American
science, enumerates the problems that have resulted, and suggests
that at the present time policy fiats and changes in the law
seeking to correct the problems "are very likely doomed to have
overly broad effects with harmful, unintended consequences."
QY: Lita Nelsen, Massachusetts Institute of Technology, 617-253-
1000 (Science 6 Mar 98)

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

Related Background:
MORE PROBLEMS ARISING FROM CORPORATE-UNIVERSITY RESEARCH TIES
Difficulties with corporate support of university research were
in the news again this week. In general, what is happening is
that legal tangles in patents and licenses are slowing or halting
completely the availability of technology needed in the diagnosis
and treatment of various diseases. Abbott Laboratories and
Perkin-Elmer Applied Biosystems are in a squabble about a new
nucleic acid analyzing machine called TaqMan that holds great
promise for AIDS researchers, and Paul Jung, an organic chemist
at Abbott, was recently stopped by his employer from giving a
scheduled paper on TaqMan at a meeting. In another domain, a
cell-sorting device made by CellPro Inc. of Seattle is being
suppressed by its competitor, the triumvirate Becton Dickinson
and Co., Baxter Healthcare Corp., and Johns Hopkins University.
This device is used to sort healthy stem cells, and is of great
importance for people undergoing cancer chemotherapy. Third, in
the domain of DNA research, Stanford University has evidently
awarded an exclusive license for the manufacture and sale of a
powerful new machine that makes oligonucleotides (short stretches
of the nucleotides that are the building blocks of DNA), and the
company, Protogene (Palo Alto, CA US), which is backed by Life
Technologies (Gaithersburg, MD US), refuses to sell the machine
to anyone. Protogene is apparently interested in maintaining a
price floor in the cost of the oligonucleotides that are
essential for DNA research. (Science 6 Jun 97)

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UNIVERSITY OF CALIFORNIA LOSES IMPORTANT INSULIN PATENT LAW SUIT
After a 7 year battle, the University of California (US) has lost
an important patent infringement law suit with the result that
the university will receive no royalties and incur its own legal
costs of $12 million. This is a complicated story that begins in
1977 with the sequencing of the rat insulin gene by William
Rutter and Howard Goodman, then at the University of California
San Francisco, at a time when there were tight Federal regula-
tions concerning what could or could not be done in recombinant
DNA technology. In the early stages of the rat insulin work,
Rutter and Goodman apparently used a modified plasmid that had
not been approved by the U.S. National Institutes of Health. They
say now they switched to an approved vector and used results from
that research as the basis for the publication and patent applic-
ations. In 1990, the University of California sued the Eli Lilly
Co., which has been involved with recombinant DNA insulin
production for many years, the university claiming patent
infringement. A U.S. District Court ruled in favor of Lilly. Last
month, the U.S. Court of Appeals for the Federal Circuit upheld
the lower court ruling. This case is now called by some patent
experts "yet another illustration of the poor match between
academic research and the patent system". Some also believe that
after this ruling researchers who obtain patents on animal DNA
sequences will not be able to claim proprietary rights over
similar or identical sequences in human DNA. One has the feeling
we are only beginning the era of serious imbroglios in the legal-
commercial arena in which much of biotechnology is now practiced
by both universities and corporations. (Science 22 Aug 97)


2. XENOTRANSPLANTATION: A GROUP OF LETTERS
Xenostransplantation involves the surgical replacement of
defective human organs by animal organs. There are at present two
primary concerns in this area: 1) The use of genetically
engineered animal organs is of great appeal because human organs
are usually rejected by the human immune system, and a patient
receiving a human organ must be on a lifetime regimen of immune-
system-suppressant drugs; and 2) the possibility that the genome
of the animal cells may contain the sequences of endogenous
viruses, and these sequences may result in the appearance of
pathogenic viral forms dormant in the animal but suddenly active
in the human, and then be transmitted from human to human with
pandemic consequences. ... ... In a group of 3 letters from 5
authors in the journal Nature, various views are presented
concerning potential benefits and dangers of xenotransplantation.
A.S. Daar (Sultan Qaboos University, OM) suggests that
containment of xenotransplantation induced viral diseases may
work in the US, but any epidemic that starts may involve
countries other than the US, and that the problem is therefore
global rather than national. Salomon et al (3 installations, US),
representing the American Society of Transplant Physicians and
the American Society of Transplant Surgeons reject the call for a
moratorium on clinical trials of xenotransplantation in the US.
P. Macchiarini (Hopital Marie-Lannelongue Paris-Sud, FR) suggests
that virologists opposed to xenotransplantation clinical trials
have never been at the bedside of patients, and "cannot feel the
frustration of patients who die while waiting for an organ..."
(Nature 5 Mar 98)

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

Related Background:
... This week the U.S. Food and Drug Administration hosted a
meeting to reduce an apparent conflict between surgeons and
virologists over how to proceed. In brief, the surgeons want
accelerated research to produce genetically engineered animal
organs that will not be rejected by the human immune system,
while the virologists are not at all happy with the idea, and are
urging extreme caution in the use of animal tissues in
transplantation surgery. The animal organs of most relevance are
those from the pig, and it has already been demonstrated that pig
retrovirus can be infectiously transmitted to human cells. On the
other hand, it has also been demonstrated that the surfaces of
pig cells can be easily genetically engineered so that organ
rejection might be eliminated. Despite the conflict, and the real
danger of endogenous virus infections, the need for artificial
organs is so great there is a consensus that the field of
xenotransplantation will move forward no matter what the
obstacles. (Nature 31 Jul 97) 

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MORE CONTROVERSY CONCERNING POLICY ON XENOTRANSPLANTS
Organ xenotransplantation is the transplantation of organs from
one species into another species, and in particular the
transplantation of animal organs into humans. In the context of
this report, "xenotransplantation" refers to animal-to-human
organ transplantation. As immunologists and molecular biologists
achieve increasing control over the biology of the
transplantation process, there has been a running debate about
the relative weights of the benefits and dangers of animal-to-
human transplantation (cf. related background reports below). In
an editorial and several associated articles, the journal Nature
is now calling for an international moratorium on clinical trials
involving xenotransplantation, saying "a well-organized and
informed public debate should precede any action by regulatory
agencies." In a letter in the same issue of the journal, Bach and
Fineberg (Harvard University, US) also call for a moratorium "on
all forms of clinical xenotransplantation".
QY: Fritz H. Bach {fbach@bidmc.harvard.edu} (Nature 22 Jan 98)

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IDENTIFICATION OF HUMAN-TROPIC PIG RETROVIRUSES
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. In
some viruses, this incorporated DNA may remain dormant for some
time before it is activated and the viral replication process
begins. HIV is one such virus. Concerning retroviruses, if the
incorporation of the viral DNA into the host cell DNA takes place
in germ-line cells (oocytes) or early embryos, then the retro-
viral genes become "endogenous" -- they become a permanent part
of the organism genome and are reproduced from generation to
generation. It is believed by some that all vertebrates, for
example, have endogenous retroviruses that are the "footprints"
of ancient retroviral infections. For the most part, the
significance of endogenous retroviruses is unclear, but there is
some evidence suggesting they may contribute to the development
of diseases in several animal species. Endogenous retroviruses
have been in the news recently in connection with organ xeno-
transplantation, the transplantation of animal organs into
humans. Some virologists are concerned that deleterious animal
endogenous retroviruses might be activated following transplant-
ation into the human body. Now Paul Le Tissier et al (5 authors
at 2 installations, UK) report the discovery of two different
classes of porcine (pig) endogenous viruses in a variety of
normal porcine tissues that are capable of infecting human cells.
The authors suggest that the breeding of virus-free pigs, if at
all feasible, will be a complex task.
QY: Jonathan P. Stoye {jstoye@nimr.mrc.ac.uk}
(Nature 16 Oct 1997)


3. NEAR-CLOSURE OF A UNIVERSITY CHEMIST PLAGIARISM CASE
The US National Science Foundation (NSF) and prominent Ohio State
University chemistry professor Leo A. Paquette have apparently
agreed to a legally binding settlement, in which Paquette
excludes himself from receiving any federal funding for the next
2 years, while NSF agrees not to issue a finding of scientific
misconduct. NSF evidently concluded that Paquette violated the
integrity of the peer review process by lifting background
material from a proposal he had reviewed for NSF and publishing
the material in the Journal of the American Chemical Society in
1992. During the investigation of the case there were also
charges against Paquette of obstruction of a federal investigat-
ion after he submitted falsified evidence to the agency. Paquette
admits the evidence was falsified, and his secretary has claimed
responsibility for it. Ohio State University has agreed with NSF
that Paquette improperly used material from an NSF proposal. The
university's chemistry department, however, considers the
plagiarism charge insignificant, saying that Paquette's actions
"could be considered sloppy, but do not constitute plagiarism by
most definitions." The material lifted from the NSF proposal
appeared only in the introductory paragraphs of Paquette's
published paper. NSF's General Counsel has stated Paquette "poses
too great a business risk to receive government funding."
QY: Linda Raber
edit.cen@acs.org
(Chem. & Eng. News 9 Mar 98)


4. WOMEN NOW SUBSTANTIAL PORTION OF ALL NEW US CHEMISTS
The latest survey of the American Chemical Society, covering
chemists and chemical engineers who graduated between July 1996
and June 1997, shows the following statistics for new women
graduates (percentage of total graduates who are women):
Chemistry Bachelor's Degree: 48.2%
Chemistry Master's Degree: 46.2%
Chemistry PhD Degree: 31.6
Chemical Engineering Bachelor's Degree: 35.4%
Chemical Engineering Master's Degree: 29.3%
Chemical Engineering PhD Degree: 22.9%
QY: Michael Heylin
edit.cen@acs.org
(Chem. & Eng. News 9 Mar 98)


5. A GLOBAL APPROXIMATION TECHNIQUE FOR MULTIVARIATE SYSTEMS
The term "statistical mechanics" (also known as statistical
thermodynamics) is a branch of physics concerned with explaining
and predicting the macroscopic behavior and properties of a
system from the known characteristics and interactions of the
microscopic constituents. Although the mathematical formalism was
first applied to mechanical systems (i.e., entities in motion),
the same formalism can be applied to any system whose behavior
and properties derive from a large population of components. In
the context of this report, the term "neocortical interactions"
refers to interactions of neurons in the neocortex, the most
recently evolved parts of the mammalian cerebral cortex. The
acronym "EEG" refers to the electroencephalogram, a voltage/freq-
uency/time measurement of electric brain potentials that can be
recorded with external scalp electrodes, the measurements
"macroscopic" in the sense that the recorded EEG activity at any
instant derives from the behavior of extremely large numbers of
neurons. ... ... L. Ingber (Ingber Research, US) reports analyses
of three different physical systems (a neural system, a financial
system, and a military combat system) using nonlinear nonequilib-
rium multivariate statistical mechanics, the analyses involving a
numerical global optimization technique to fit experimental
empirical data to the models. A theory of statistical mechanics
of neocortical interactions, first published in 1982, is used to
correlate individual EEG measures of brain function with
attention tasks.
QY: Lester Ingber
ingber@ingber.com
(J. Math. Comput. Model. 27:9 1998)

(continued in Part 2)

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SCIENCE-WEEK - Part 2/3

A Free Weekly Digest of the News of Science

March 20, 1998

Contents of Part 2:

6. On Black Holes as Real Astronomical Objects
7. On the Geological Evolution of Venus
8. On Quantum Theory Without Observers
9. Subsurface Charge Accumulation in a Quantum Hall Liquid
10. A New Technique for Size Separation of Macromolecules
11. Hydrogen Hypothesis for the First Eukaryote
12. Polyketide Synthases as Modular Enzymes
13. A Model for the Mechanism of a Human Topoisomerase

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

6. ON BLACK HOLES AS REAL ASTRONOMICAL OBJECTS
If the terminal stages of star death leave a remnant star mass
greater than 3 solar masses, the ultimate gravitational collapse
will produce a "black hole", a relativistic singularity. A black
hole is a localized region of space from which neither matter nor
radiation can escape. The Uhuru Satellite (uhuru is the Swahili
word for "freedom"), launched in 1970 and operating until 1973,
was the first artificial satellite for x-ray astronomy, producing
a catalogue containing 339 x-ray sources. ... ... G. Bisnovatyi-
Kogan (Space Research Institute Moscow, RU) reviews the papers
presented at a recent international conference on black holes
(11-17 January 1998, S.N. Bose National Centre for Basic Sciences
Calcutta, IN). This was perhaps the first conference devoted to
black holes as real astronomical objects. The first indications
for the actual existence of black holes came from x-ray observ-
ations of the UHURU satellite, but black holes were predicted
theoretically 60 years ago, and in fact Laplace in 1796 already
noted that light cannot leave a star when its free-fall velocity
as determined by the star's mass and radius is larger than the
speed of light as we have measured it. At the present time, if
the apparent mass of a discovered compact object exceeds the
limiting mass, and if we hold the theory of general relativity to
be valid, we say we have discovered a black hole. There are now
40 such objects that have been identified, 30 of them super-
massive objects each containing millions and billions of solar
masses and surrounded by dense stellar clusters in the strong
gravity of a black hole.
QY: G. Bisnovatyi-Kogan 
gkogan@mx.iki.rssi.ru
(Science 27 Feb 98)


7. ON THE GEOLOGICAL EVOLUTION OF VENUS
Seismic studies indicate the interior of the Earth consists of
three parts: a hot metallic core, a dense rocky mantle, and a
thin low-density crust. The central part of the core is solid,
but the outer part of the core is evidently liquid. In geology, a
"dome" is a circular or elliptical upfold type of structural
deformation; a "rise" is a long and broad elevation rising gently
from its surroundings; "mantle plumes" are thin vertical conduits
of molten rock material from the core-mantle boundary to the
crust. The term "lithosphere" refers to the outer layer of the
Earth, comprising the crust and upper mantle, and extending to a
depth of 50 to 70 kilometers. All of these terms have applicat-
ions in the study of the geology of other planets.... ...
Phillips and Hansen (2 installations, US) review extant data
concerning the geology of crustal plateaus and volcanic rises on
Venus, and present a model for their formation, and a model of
the thermal evolution of the lithosphere of Venus. The authors
suggest that crustal plateaus and volcanic rises on Venus formed
as a result of the interaction with the lithosphere of mantle
plumes rising from the core-mantle boundary, and that the climate
and internal history of Venus were strongly coupled throughout
much of its history. QY: Roger J. Phillips, Washington Univ. St.
Louis, Dept. of Earth and Planetary Sciences 314-935-5610
(Science 6 Mar 98)


8. ON QUANTUM THEORY WITHOUT OBSERVERS
One of the fundamental questions of physics is whether pure
states (i.e., states undisturbed by avoidable noise) are states
such that the outcome of every measurement can be exactly
predicted. Classical physics is based on the proposition that the
answer to the question is yes. Orthodox quantum mechanics is a
theory based on the proposition that the answer is no, and that
we can only make precise quantitative statements about probab-
ilities, the limitation due to an essential interaction between
the observer and that which is being measured.
... ... S. Goldstein (Rutgers University New Brunswick, US), in
the first of a two-part review, discusses the idea of quantum
theory without observers, and suggests that despite the claims of
most of the originators of quantum theory, the appeal at a fund-
amental level to observers and measurement, which is so prominent
in orthodox quantum theory, is not needed to account for quantum
phenomena. Referring to the classical Bohr-Einstein debate,
Goldstein says the debate has already been resolved in favor of
Einstein. What Einstein desired and Bohr held impossible -- an
observer-free formulation of quantum mechanics in which the
process of measurement can be analyzed in terms of more fund-
amental concepts, does in fact exist, and there are many such
formulations, several of which have the potential to become a
serious program for the construction of a quantum theory without
observers. QY: Sheldon Goldstein, Rutgers University New
Brunswick 908-932-8789 (Physics Today March 1998)


9. SUBSURFACE CHARGE ACCUMULATION IN A QUANTUM HALL LIQUID
In classical physics, the Hall effect is the development of a
transverse voltage across a current-carrying conductor in a
magnetic field, the voltage being perpendicular to both the 
direction of the current and the direction of the magnetic field.
In quantum physics, there are two other Hall effects, an integer
charge quantum Hall effect, and a fractional charge quantum Hall
effect, these quantum Hall effects being observed at extremely
low temperatures (a few degrees Kelvin) and extremely high
magnetic fields (at least several tesla). Both quantum Hall
effects were first noted in the 1980s. In the quantum Hall
effect, the Hall resistance, the ratio of the voltage to the
current, is precisely related to Planck's constant, the
electronic charge, and an integer or rational fraction. In the
context of this report, the subsurface charge accumulation probe
measures the local accumulation of charge in a 2-dimensional
electron system in response to an applied AC (alternating
current) excitation. ... ... Tessmer et al (5 authors at 2
installations, US) report a cryogenic scanning probe technique
("subsurface charge accumulation" imaging) that permits very high
resolution examination of systems of mobile electrons inside
materials, and the use of this technique to image directly the
nanometer-scale electronic structures that exist in the quantum
Hall regime. The authors suggest this new technique has a
profound capability to examine systems that have been
inaccessible to imaging with comparable resolution.
QY: R.C. Ashoori
ashoori@mit.edu
(Nature 5 Mar 98)

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

Related Background:

RESOLUTION OF FRACTIONAL CHARGE QUANTUM HALL EFFECT
... The fractional quantum Hall effect, although experimentally
observed, has not been theoretically resolved. In 1982, Robert
Laughlin postulated the theoretical existence of quasi-particle
excitations with fractional charge e/3, where e is the
conventional electronic charge, the quasi-particle being the
statistical result of the collective motion of many electrons.
Now R. de-Picciotto et al (Weizmann Institute of Science, IL),
measuring the fluctuations of a small current flowing through a
specially designed quantum point contact in a two-dimensional
electron gas using a shot noise technique, have apparently
demonstrated unambiguously the existence of quasi-particles with
fractional charge as predicted by Laughlin's theory. Fractional
charge, albeit that of a quasi-particle, is thus no longer unique
to the domain of elementary particle physics. The authors state,
"The magic of an apparent smaller charge due to electron-electron
interactions is a beautiful manifestation of the strength of the
theoretical methods used to predict such counterintuitive
behavior." QY: R. de-Picciotto {hrafi@wis.weizmann.ac.il}
(Nature 11 Sep 97)

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

... The importance of the classical Hall effect, discovered by E.
H. Hall in 1879, is that it indicates the sign of the charge
carriers in a conductor. Hall placed a metal strip carrying a
current in a magnetic field, and observed a voltage difference
produced across the strip. The side of the strip at the higher
voltage depends on the sign of the charge carrier, and Hall's
observations demonstrated that in metals the charge carriers are
negative. It was only later that the metal charge carriers were
identified as electrons. The Hall effect again became an active
area of research with the discovery of the quantized Hall effect
by Klaus von Klitzing, who received the Nobel Prize in Physics
for his discovery in 1985. Before von Klitzing's discovery, it
was believed that the amount of voltage difference across the
conducting strip varied in direct proportion to the strength of
the magnetic field. Von Klitzing demonstrated that under the
special conditions of low temperature, high magnetic field, and
two-dimensional electron systems in which electrons are confined
to move in a plane, the voltage difference is quantized,
increasing in a series of steps with increasing magnetic field.
(Science-Report 26 Sep 97)


10. A NEW TECHNIQUE FOR SIZE SEPARATION OF MACROMOLECULES
Electrophoresis is an electrochemical process in which colloidal
particles or macromolecules with a net electric charge migrate in
a solution under the influence of an electric field. In the
context of this report, "microlithography" is the general term
for the technique used to fabricate microscale circuits on
silicon chips, the technique essentially involving exposure of an
intervening attached light-sensitive film through a template mask
as a precursor to the circuit etching process. ... ... In an
instance illustrating how technological advances in one field can
provoke essentially unpredictable technological advances in an
another field only remotely connected, a new technique for the
size separation of macromolecules has been introduced. The new
method provides an alternative to the gel electrophoresis methods
commonly used to separate proteins and DNA. The new technique
uses arrays of separation cells etched by microlithography on
silicon chips to separate macromolecules in an electrophoresis
flow stream. The method was reported recently by two independent
groups, D. Ertas (Harvard University, US), and T. Duke and R.H.
Austin (2 installations, UK US), with the first group focusing on
theoretical aspects, and the second group evaluating a practical
prototype of the device.
QY: Stephen Stinson
edit.cen@acs.org
(Chem. & Eng. News 9 Mar 98) (Phys. Rev. Lett. 80:1548,1552 1998)


11. HYDROGEN HYPOTHESIS FOR THE FIRST EUKARYOTE
The classification system of bacteria is presently in a state of
flux due to new relationships continually revealed by molecular
biology, but the following nomenclature is generally accepted.
Eubacteria is a subkingdom of bacteria. All Eubacteria members
are prokaryotes, which means they lack a membrane-bound nucleus,
structured chromosomes, and complex internal organization. The
eukaryotes, in contrast, contain membrane-bound organelles,
including a nucleus. The archaebacteria (also called the Archaea)
are a subkingdom of bacteria considered to be ancient compared to
other bacterial kingdoms, and possibly the most ancient life
forms and the ancestors of all eukaryotes. They typically exist
in extreme environments, and include the methane-producing
bacteria (methanogens), the "salt-loving" bacteria (halophilic
bacteria), and the sulfur-acid tolerant thermoacidophilic
bacteria. In biology, "symbiosis" is an intimate and protracted
association of individuals of different species, and if both
participants receive benefits from the association, it is usually
called "mutualism". The term "autotrophic" means self-feeding,
and is used to characterize organisms that can synthesize all
their necessary nutrients from the oxidation of inorganic
compounds. Autotrophs are the primary producers of organic
compounds for all "heterotrophic" organism (i.e., organisms that
feed on other organisms). The term "anaerobic" refers to the
absence of oxygen. ... ... Martin and Muller (2 installations, DE
US) present a new hypothesis for the origin of eukaryotic cells,
the hypothesis based on the comparative biochemistry of energy
metabolism. Eukaryotes are proposed to have arisen through
symbiotic association of an anaerobic, strictly hydrogen-
dependent, strictly autotrophic archaebacterium (the host) with a
eubacterium (the symbiont) that was able to respire, but which
generated molecular hydrogen as a waste product of anaerobic
heterotrophic metabolism. The host's dependence upon molecular
hydrogen produced by the symbiont is proposed as the selective
principle that forged the common ancestor of eukaryotic cells.
The authors suggest their hypothesis generates numerous testable
predictions, and they firmly predict that evidence for a strictly
H(sub2)-dependent ancestry, and most probably a methanogenic
ancestry, of the host should ultimately be revealed by
comparative genomics. They also predict that anaerobic
heterotrophic habitats devoid of geological hydrogen may harbor
eukaryotes more primitive than known forms, the metabolism of
which should be accountable for by their hypothesis.
QY: William Martin
w.martin@tu-bs.de
(Nature 5 Mar 98)  


12. POLYKETIDE SYNTHASES AS MODULAR ENZYMES
Enzymes are proteins that serve as highly specific catalysts of
various biological reactions, and there is much research underway
attempting to understand the mechanisms of enzyme catalysis and
to construct new enzymes for the specific catalysis of nonbiolog-
ical reactions. ... ... R. Rawls (Chem. & Eng. News, US) reviews
the use of polyketide synthases as modular enzymes. The polyket-
ides are a large and structurally diverse family of natural
compounds produced primarily by bacteria and fungi, with
approximately 10,000 of them identified in nature. They are all
synthesized by repetitive additions of two- or three-carbon acyl
building blocks to form a linear chain frequently cyclized after
its formation. Some commercially important polyketides are the
antibiotics erythromycin and spiramycin, the veterinary drug
avermectin, and the immunosuppressant rapamycin. These substances
are synthesized by giant multifunctional enzymes that are modular
in their structure, each module constructing a section of the
final molecule and then passing the intermediate to the next
synthesis station for the attachment of an additional section.
During the past 5 years, chemists have learned how to shuffle the
pieces of the polyketide synthases to make new molecules,
changing the enzymes functional domains to produce non-natural
products.
QY: Rebecca L. Rawls
edit.cen@acs.org
(Chem. & Eng. News 9 Mar 98)


13. A MODEL FOR THE MECHANISM OF A HUMAN TOPOISOMERASE
Topoisomerases are enzymes that facilitate the DNA unwinding
necessary for replication by introducing transient breaks in one
or both strands of the DNA double helix, with breaks subsequently
repaired. Essentially, the idea is that without this action of
topoisomerases, the entire double helix would need to rapidly
unwind in order for replication to occur segment by segment, but
with topoisomerase breaking and repair, the unwinding can occur
in sections of DNA without a complete rotation that would demand
high energies. ... ... Stewart et al (5 authors at University of
Washington, US) report an analysis of the 3-dimensional structure
of a 70 kilodalton form of human topoisomerase type 1 in complex
with a 22-base pair oligonucleotide, the structure determined to
a resolution of 2.8 angstroms, with all the structural elements
of the enzyme that contact DNA apparently revealed. The authors
suggest the topoisomerization step occurs by a mechanism termed
"controlled rotation", part of which is driven by torsional
strain within the DNA part of the complex.
QY: J.J. Champoux 
champoux@u.washington.edu
(Science 6 Mar 98)

(continued in Part 3)

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

SCIENCE-WEEK - Part 3/3

A Free Weekly Digest of the News of Science

March 20, 1998

Contents of Part 3:

14. Host Derived Amino Acids Support Symbiotic Bacteria
15. Identification of a Cell Membrane Nucleic Acid Channel
16. Plant Performance and Induced Responses to Herbivory
17. Single Neuron Control of Synaptic Efficacy
18. Characterization of an In Vitro Blood-Brain Barrier
19. Muscle Regeneration by Bone-Marrow-Derived Cells
20. Genetic Traces of Ancient Demography

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14. HOST DERIVED AMINO ACIDS SUPPORT SYMBIOTIC BACTERIA
An "auxotrophic mutant" is a species variety, usually a
microorganism, that will proliferate only when its growth medium
contains certain specific nutrients not required by the wild-type
(non-mutated) members of the species. Dozens of species of
luminous animals maintain specific associations with biolumin-
escent bacteria that are housed in specialized light-emitting
organs, and this report concerns one such association, involving
a bioluminescent bacterium whose colonies are replenished each
day by its host, a squid, the bacteria in the squid light organs
evidently multiplying during the day to reach a population of
about 10^(6), with the bioluminescence an important part of the
squid's nocturnal feeding activities. Each morning, more than 90%
of the bacteria are vented from the light organs, and the culture
cycle starts anew. ... ... Graf and Ruby (University of Southern
Calif., US), investigating the symbiotic relation between
auxotrophic mutants of the bioluminescent bacterium Vibrio
fischeri and the host squid Euprymna scolopes, report that the
host provides at least 9 amino acids to the growing diurnally
renewed cultures of symbiotic bioluminescent bacteria present in
its light-emitting organ. The authors suggest their technique of
sampling the symbionts and surrounding environment without
contamination by host tissue components, in combination with
molecular genetic studies, allows the characterization of the
nutritional conditions that support a cooperative animal-
bacterial symbiosis.
QY: Edward G. Ruby
eruby@hawaii.edu
(Proc. Natl. Acad. Sci. US 17 Feb 98)


15. IDENTIFICATION OF A CELL MEMBRANE NUCLEIC ACID CHANNEL
"Brush border" cells are a specific type of cells in the kidney. 
Lipid bilayers are spontaneously forming self-organizing
bimolecular layers of certain molecules with long nonpolar chains
terminated by a polar group. Such molecules are found in cell
membranes, and also in soaps. 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, and a proteoliposome is such
a vesicle bilayer complexed with protein. The term "voltage
clamp" refers to a method of investigating the current-voltage
characteristic of an electrically conducting system by feedback
control that maintains the voltage constant during a short step-
change in order to investigate the current that flows in
response. The method is necessary in biological systems, since
the electrical resistance (permeability) of biological membranes
is voltage-dependent, and the method is also used in artificial
membrane systems containing such variable resistances. Membrane
ion channels that can be opened or closed by voltage or chemical
events are said to be "gated". ... ... Hanss et al (5 authors at
2 installations, US) report the identification of a 45 kilodalton
protein purified from rat renal brush border membrane that binds
short single-stranded nucleic acid sequences, and that when this
activity is purified, reconstituted in proteoliposomes, and then
fused with model planar lipid bilayers, voltage-clamp experiments
indicate the reconstituted protein functions as a gated channel
that allows the passage of nucleic acids. Channel activity was
not observed if the protein was heat-inactivated prior to forming
proteoliposomes. The authors suggest these studies provide
evidence for a cell surface channel that conducts nucleic acids,
and raise the intriguing question of what is the endogenous
function of a cell surface nucleic acid channel?
QY: Basil Hanss 
b.hanss@smtplink.mssm.edu
(Proc. Natl. Acad. Sci. US 17 Feb 98)


16. PLANT PERFORMANCE AND INDUCED RESPONSES TO HERBIVORY
Herbivores are animals that feed on plants, and "herbivory" is
plant-eating. Induced plant responses to herbivory are immune-
like responses of plants to plant-feeding that reduce the
performance and/or preference of herbivores for plants, and have
been reported from over 100 plant-herbivore systems. These
responses are assumed to benefit plants, although such benefits
have never been demonstrated in a field experiment. The term
"phloem" refers to the tissue in a vascular plant through which
the sap containing dissolved food materials passes downward to
the stems and roots. ... ... A. Agrawal (University of California
Davis, US), in a study of induced plant resistance to herbivores
in a field experiment (wild radish: Raphanus sativus L. Brassic-
aceae), reports that induction early in the season resulted in
halving of herbivory by chewing herbivores and a reduction in the
abundance of phloem-feeding aphids when compared with controls.
Seed mass, a correlate of lifetime plant fitness, was enhanced by
over 60 percent for individuals that were induced. The author
suggests that induced defense is a strategy that may be favored
by natural selection in environments with herbivory.
QY: A. Agrawal
aaagrawal@ucdavis.edu
(Science 20 Feb 98)


17. SINGLE NEURON CONTROL OF SYNAPTIC EFFICACY
The junctions between nerve cells, and between nerve cells and
muscle cells, are called "synapses", and the term "synaptic
efficacy" refers to the ability of a presynaptic input to provoke
a postsynaptic response. Neurotransmitters are chemical
substances released at the terminals of nerve axons in response
to the propagation of an impulse to the end of that axon. The
neurotransmitter substance diffuses into the synapse, the
junction between the presynaptic nerve ending and the
postsynaptic neuron, and at the membrane of the postsynaptic
neuron the transmitter substance interacts with a receptor.
Depending on the type of receptor, the result may be an
excitatory or an inhibitory effect on the postsynaptic nerve
cell. Synaptic vesicles are the packets of neurotransmitter
substance formed in the presynaptic axon terminals, and when
transmitter substances are released, they are released as
packets, the vesicle membrane dissolving in the synaptic space to
release the transmitter molecules. The term "quantal transmitter
release" has nothing to do with quantum mechanics, and refers
merely to the fact that vesicles released at the synapse are all
about the same size, containing approximately the same number of
transmitter molecules, and each packet of transmitter molecules
apparently produces a unit effect on the postsynaptic membrane.
... ... Davis and Goodman (University of California Berkeley,
US), in a study involving genetic manipulation of muscle
innervation in the fruit fly Drosophila, report that there are
two independent mechanisms by which muscle regulates synaptic
efficacy at the terminals of single motor neurons, and that
increased muscle innervation results in a compensatory target-
specific decrease in presynaptic transmitter release, while
decreased muscle innervation results in a compensatory increase
in quantal size of transmitter release. The authors suggest these
newly revealed regulatory processes may have relevance for a
variety of human clinical disorders.
QY: G.W. Davis
gdavis@coreys.berkeley.edu
(Nature 5 Mar 98)


18. CHARACTERIZATION OF AN IN VITRO BLOOD-BRAIN BARRIER
The blood brain barrier is an extremely thin tissue barrier that
prevents many molecules and substances from free diffusion or
transport into brain tissues or cerebrospinal fluid from the
blood stream, brain interarterial fluid thus being separated from
circulatory blood. Endothelial cells are a variety of cells that
form flat layers (endothelia) lining the heart and vessels such
as blood vessels and lymphatic vessels. In general, dialysis is
any filtration process using a semipermeable membrane to separate
large molecules from small molecules based on their permeability
through the membrane. ... ... Duport et al (6 authors at Centre
Medical Universitaire Geneva, CH) report a new in vitro blood-
brain barrier involving organotypic slice cultures from the
central nervous system overlaid on endothelial cell monolayers
grown on permeable membranes, with morphological, electrophysio-
logical, and microdialysis approaches used to characterize the
model. Results indicate the in vitro model has characteristics
similar to the blood-brain barrier in situ. The authors suggest
that cocultures of organotypic slices and endothelial cell
monolayers are potentially powerful tools for studying
biochemical mechanisms regulating blood-brain barrier function
and drug delivery to the central nervous system.
QY: L. Stoppini luc.stoppini@medicine.unige.ch
(Proc. Natl. Acad. Sci. US 17 Feb 98)


19. MUSCLE REGENERATION BY BONE-MARROW-DERIVED CELLS
"Immunodeficient mice" are mice genetically engineered to have a
reduced immune response, and "myogenic differentiation" refers to
precursor unspecialized cells becoming specialized in form and
function as muscle cells. The muscular dystrophies comprise a
number of hereditary progressive degenerative disorders affecting
skeletal muscles and often other organ systems. ... ... Ferrari
et al (7 authors at 3 installations, IT) report that transplant-
ation of genetically marked bone marrow into immunodeficient mice
reveals that marrow-derived cells migrate into areas of induced
muscle degeneration, undergo myogenic differentiation, and
participate in the regeneration of the damaged fibers. The
authors suggest that genetically modified, marrow-derived
myogenic progenitors might be used to target therapeutic genes to
muscle tissue, thus providing an alternative strategy for the
treatment of the muscular dystrophies.
QY: Giulio Cossu 
cossu@axrma.uniroma1.it
(Science 6 Mar 98)


20. GENETIC TRACES OF ANCIENT DEMOGRAPHY
The term "haploid loci" refers to genome locations that derive
from only one parent. Mitochondrial DNA (sometimes denoted as
mtDNA), found in the mitochondria of all eukaryotes, is believed
to evolve in parallel with nuclear DNA, but since sperm lose
their mitochondria, it is inherited only in the maternal lineage
in animals. Mitochondrial DNA has been greatly exploited in
studies of the evolution of humans. A "nonrecombining" part of a
genome is a part that does not vary when the entire genome is
replicated during reproduction. The Pleistocene is the geological
time period from about 2 million years ago to about the end of
the last glaciation about 10,000 years ago. Modern man is
believed to have evolved during the Pleistocene.
... ... Harpending et al (6 authors at 3 installations, US), in a
study of the demographic history of the human species as revealed
by patterns of gene differences, report that haploid loci like
mitochondrial DNA and the nonrecombining part of the Y chromosome
show a pattern indicating expansion from a population of only
several thousand during the late middle or early upper
Pleistocene. The authors suggest our ancestral population size
during nearly the whole Pleistocene was of the order of 10,000
breeding individuals, and that genetic evidence denies any
version of the multiregional model of modern human origins, and
implies instead that our ancestors were effectively a separate
species for most of the Pleistocene, a small population probably
occupying an area the size of Swaziland or Rhode Island rather
than a whole continent. The authors further suggest that
archeologists should find and identify this population.
QY: Henry C. Harpending
harpend@ibm.net
(Proc. Natl. Acad. Sci. US 17 Feb 98)

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BOOK NOTES:

D. Blair and G. McNamara: RIPPLES ON A COSMIC SEA
The Search for Gravitational Waves
Addison-Wesley, 1998, 208p, US22
For the general reader. A narrative of the race to build the
first gravitational wave antenna. David Blair is a physicist
specializing in gravitational waves; Geoff McNamara is a science
journalist.

John L. Casti: THE CAMBRIDGE QUINTET
A Work of Scientific Speculation
Addison-Wesley, 1998, 208p, US23
An imaginary evening in the year 1949 at Cambridge University
with five of the great intellectuals of the 20th century:
Wittgenstein, Snow, Haldane, Schrodinger, and Turing. A narrative
tour-de-force in which the characters argue whether machines
will
ever have the ability to think like humans -- and whether they
should be allowed to do so. The author is a science journalist.

R. Clay and B. Dawson: COSMIC BULLETS
High Energy Particles in Astrophysics
Addison-Wesley, 1998, 208p, US22
A narrative of the discovery and study of cosmic rays from deep
space. The authors are both cosmic ray physicists.

Richard P. Feynman: THE MEANING OF IT ALL
Thoughts of a Citizen Scientist
Addison-Wesley, 1998, 224p, US24
Based on a previously unpublished 3 part public lecture at the
University of Washington (US) in 1963. Feynman expounding on the
inherent conflict between science and religion, popular distrust
of politicians, universal fascination with flying saucers, faith
healing, mental telepathy, the English language, the death of his
first wife from tuberculosis. Feynman reflective, amusing, ever
enlightening.

H. Kuzmany: SOLID-STATE SPECTROSCOPY
An Introduction
Springer, 1998, 480p, US64.95
A graduate text. Theory, methods, and applications of
spectroscopic techniques; latest advances with lasers and
synchrotrons; Fourier transform spectroscopy; pulsed and magnetic
NMR techniques; photoemission; light and electron scattering.

A. M. Zagoskin: QUANTUM THEORY OF MANY-BODY SYSTEMS
Techniques and Applications
Springer, 1998, 248p, US49.95
A graduate text. A self-contained treatment of the physics of
many-body systems from the point of view of condensed matter.
Diagram techniques for normal and superconducting systems. Uses
mathematical formalisms of quasiparticles and Green's functions.
Examples from mesoscopic physics.

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