|
ScienceWeek
SCIENCE-WEEK - Part 1
A Free Weekly Digest of the News of Science
January 9, 1998
-----------------------------------------------
"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
-----------------------------------------------
Contents of This Issue:
Part 1:
1. Obesity and Mortality: Spinning Science News
2. Cancer: Questions Concerning Research Non-Treatment in India
3. Another Scientific Fraud Scandal in Germany
4. Quantum Mechanics and Cosmology
5. Gamma Ray Bursts and Possible Terrestrial Disaster
6. Semiconductor-Polymer Interface Tunable Diode
7. Localization of Light in a Disordered Medium
8. Quantum-Confined Stark Effect in Crystallite Quantum Dots
9. A Method for Patterning of Orientated Mesoscopic Domains
10. Analysis of Monolayer Film Catalysis
Part 2:
11. Synthesis of Multidimensional Large-Cage Zeolite Structures
12. Selection of Broad-Scope Enzymes by Antibody Catalysis
13. Analysis of Intracellular Signaling Mechanisms
14. Abscisic Acid Signaling in Plants
15. Evidence for Cyclic AMP Signaling in Higher Plants
16. Transgenic Sheep Expressing Human Clotting Factor Protein
17. More Evidence that Prion Protein Binds Copper In Vivo
18. Involvement of Immune System B-Cells in a Prion Disease
19. Regeneration of Axons in Central Nervous System White Matter
20. Animal Models of HIV-1 Disease
---------------------------------------------
1. OBESITY AND MORTALITY: SPINNING SCIENCE NEWS
Stevens et al (6 authors at 4 installations, US), in a study of
the mortality of 62,116 men and 262,019 women during a 12 year
period (1960-1972), report that excess body weight increases the
risk of death from any cause and from cardiovascular disease in
adults between 30 and 74 years of age, and that the relative risk
associated with greater body weight is higher among younger
subjects. The above words are essentially the exact conclusions
chosen to be published by the authors. Nevertheless, two variants
of contrary journalistic "spin" have appeared, an interesting
illustration of how public health news is formulated. In the
first variant, in an editorial in the same journal in which the
Stevens et al report appeared, two journal editors emphasize that
the mortality increase with body-mass is modest and age-depend-
ent, and they urge an end to people "suffering immeasurable
torment in fruitless weight-loss schemes and scams." In the
second variant, published by the New York Times and echoed by
many newspapers across the US, news items took note of the
journal editorial and went a step further in headlines suggesting
excess weight has now been shown to be harmless. The spin-logic
in the case of both the journal editors and the news media is
apparently that since the effect is small, the public can well
disregard it. The researchers and authors of the article,
however, apparently believe otherwise, and the last sentence of
their article is unequivocal: "In healthy white adults below the
age of 75 who have never smoked cigarettes, our results are
consistent with the healthy weight ranges proposed in the 1995
Dietary Guidelines for Americans." QY: June Stevens, Univ. of
North Carolina, Dept. of Epidemiology 919-966-7458
(New England J. Med. 1 Jan 98)
2. CANCER: QUESTIONS CONCERNING RESEARCH NON-TREATMENT IN INDIA
In India, there is an apparent uproar concerning charges that
investigators in a past cancer research project deliberately
withheld treatment from 1,107 women with uterine cervical
dysplasias when it was known that some of the lesions could
become cancerous. 69 women progressed to malignancies and had to
have cancer treatment or uterus removal, 2 women died of
radiation treatments, and 10 other women with advanced dysplasias
are still unlocated for follow-up. The women, mostly poor and
illiterate, had evidently not given their written consent to
participate in the experiment. In general, dysplasia refers to
any abnormal tissue change, and cervical dysplasia refers to a
recognizable lesion in the cervix of the uterus. At the present
time, minimal cervical dysplasia is considered a definite initial
condition in a progression to cervical invasive cancer. The
indicated research project in India was conducted between 1976
and 1988 by the Indian Council of Medical Research for the
purpose of identifying risk factors in the transformation of
dysplasias into cervical cancer. Standard manuals for diagnosis
and treatment at that time (for example, Krupp and Chatton 1982)
unequivocally recommended prompt removal of cervical dysplasia
lesions as a preventive for invasive cervical carcinoma. N.P.
Gupta, formerly Deputy Director General of the Indian Council for
Medical Research, says, "I did not know that such a study was
going on. We are all criminals." (Nature 18/25 Dec 97)
3. ANOTHER SCIENTIFIC FRAUD SCANDAL IN GERMANY
The year 1997 was apparently not a good year for professional
science in Germany. At the beginning of the year there occurred
the eruption of a fraud scandal in molecular biology, and at the
end of the year there is a new scandal in the field of experi-
mental surgery. This time a researcher at the University of
Dusseldorf, Meinolf Goertzen, has been accused of fraud in
connection with a paper published in the Journal of Bone and
Joint Surgery, a report of the effect of gamma-irradiation on the
viability of knee ligament grafts in foxhounds. There are three
co-authors, two of whom apparently deny any knowledge of the
paper, while the third co-author, the head of Goertzen's depart-
ment, claims merely "honorary" authorship. Apparently, one of the
electron-micrographs in the paper purports to demonstrate neuron
reinnervation of a non-irradiated graft in dogs, but the figure
was recognized (by the original researcher) as having been lifted
from a 1989 paper, and shows human stretch receptors in ligaments
and not dog nerve endings. Goertzen has had his "Habilitation",
the credential required for teaching in universities in Germany,
Switzerland, and Austria, rescinded by the University of
Dusseldorf, and he is now suing the institution. (Nature 18/25
Dec 97)
4. QUANTUM MECHANICS AND COSMOLOGY
The big bang theory is the general cosmological model that
proposes that all matter and radiation in the universe originated
in an explosion at a finite time in the past, and the "hot-big-
bang" theory is the specific version proposed by George Gamow in
the 1940s in which the temperature of matter and radiation
decreases with time. Quantum fluctuations are probabilistic
variations in density of quantum particles, even in a vacuum, the
variations due to the intrinsic probabilistic properties of
quantum systems. In theory, quantum fluctuations in a vacuum, for
example, involve the extremely rapid appearance and disappearance
of quantum particles -- a probabilistic birth and annihilation of
mass. The inflationary model of the early universe, first
proposed by Alan Guth in 1980, proposes that quantum fluctuations
in the time period 10^(-35) to 10^(-32) seconds were quickly
amplified into large density variations during the "inflation-
nary" 10^(50) expansion of the universe in that time frame. E.
Kolb (Univ. of Chicago, US), in a review of the relation between
quantum mechanics and present cosmological theory, points out
that already in 1937 Neils Bohr understood that advances in
cosmology would require advances in our understand-ing of quantum
mechanics. One of the more important ideas in contemporary
cosmological theory is that primordial quantum fluctuations soon
after the big bang were inflated to macroscale density
inhomogeneities that became the seeds of the gravitat-ional
clusterings that eventually led to the birth of stars and
galaxies. QY: Edward Kolb, Univ. of Chicago, Dept. of Astro-
physics 312-702-9808 (Astronomy February 1998)
-------------------
Related Background:
FAILURE OF COSMOLOGICAL DEFECT THEORY
One of the important problems in cosmology is to explain the
density inhomogeneities present in the universe, the large
structures of galaxies and networks of galaxies. There are 2
major theories, and they both involve descriptions of the first
few moments of the history of the universe, the time before about
10^(-30) seconds. One theory of structure comes out of the so-
called inflationary model of the initial universe. ... The other
theory of early structure involves a defect model in which the
initial density variations were produced by structure "seeds",
defects and misalignments in the fabric of space analogous to
those found in rapidly cooling solids. Both theories of early
structure can produce quantitative predictions of present
cosmological measurements, the prime quality of any useful
theory. One measurement of importance is the cosmic microwave
background radiation, and the present important instrument for
this is the Cosmic Background Explorer (COBE), a NASA satellite
orbited in 1989 and dedicated to such measurements. Now Neil
Turok et al (3 authors at 2 installations UK, US) report that
comparison of calculations based on the defect model with data on
the microwave background made by the COBE satellite indicate the
predictions of the defect model are in error by a factor of 2,
and the consensus is that the defect model must be abandoned. One
of the founders and important proponents of the defect model,
Turok points out the new results are "a great success", since the
destruction of a theory by evidence is a demonstration that
progress is being made. QY: N. Turok, Cambridge Univ., UK
(Physical Rev. Lett. 1 Sep 1997) (Science 24 Oct 97)
5. GAMMA RAY BURSTS AND POSSIBLE TERRESTRIAL DISASTER
Gamma rays are radiation of high energy, from about 10^(5)
electronvolts to more than 10^(14) electronvolts -- radiation
with the shortest wavelengths and highest frequencies, the gamma
ray region of the electromagnetic spectrum merging into the
adjacent lower energy x-ray region. Gamma ray bursts are intense
flashes of gamma rays detected at energies up to 10^(6) electron
volts. 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. The average density of a
neutron star is 10^(15) grams per cubic centimeter, and the
weight of an object on the surface of a neutron star would be
10^(11) its weight on the surface of the Earth. Neutron stars
apparently have an outer shell of iron, but it is iron like no
Earth iron, an iron of 4 orders of magnitude greater density.
Theory predicts that a neutron star should rotate very rapidly,
be extremely hot, and have an intense magnetic field. Leonard and
Bonnell (US National Aeronautics and Space Administration, US),
in a review of gamma ray bursts and the important data on these
phenomena collected during 1997, point out the following: 1) The
current consensus is that gamma ray bursts are produced by the
merger of two neutron stars; 2) up to this point, the bursts that
have been noted apparently originate outside our own galaxy; 3)
considering the known neutron stars inside our own galaxy, a case
can be made that evolutionary disjunctions in Earth's past may
have been caused not only by asteroid impacts, but also by gamma-
ray bursts from merging neutron stars a few thousand light years
distant in our galaxy. QY: Peter J.T. Leonard, NASA Goddard Space
Flight Center, Greenbelt, MD US (Sky & Telescope February 1998)
-------------------
Related Background:
EVIDENCE FOR DISTANT SOURCE OF GAMMA RAY BURSTS
Gamma Ray Bursts have been much in the news recently. They were
first accidentally discovered some 30 years ago by military
satellites, and then interest was rekindled when the Compton
Gamma Ray Observatory was launched by NASA in 1991. The Compton
orbiting device has been detecting Gamma Ray Bursts in all parts
of the sky on a daily basis. One controversy among astronomers
is whether the source is within our galaxy or extra-galactic.
Now Mark R. Metzger, leader of a team at the California
Institute of Technology (Pasadena CA US), reports that the
bursts detected here are coming to us through a stellar gas
cloud about 7 billion light-years away, which means the source
of the bursts must be at least that far, certainly
extra-galactic, and travelling to us for about half the age of
the universe. At least one part of a 30 year old puzzle has
apparently been solved -- the source of the bursts.
(UPI 15 May 97)
---------------------
DETECTION OF X-RAY AFTERGLOW ASSOCIATED WITH GAMMA-RAY SOURCE
Gamma ray bursts (GRBs) continue to tantalize astrophysicists.
The distribution of these bursts is isotropic across the sky, but
inhomogeneous in space, and with a deficit of faint bursts. The
problem is that present gamma ray telescopes have poor imaging
capabilities, and the phenomenology is unusual in that the bursts
last only from a fraction of a second to hundreds of seconds. At
present, it is not clear whether the bursts are produced in our
own galaxy or at cosmological distances. This week Costa et al (a
team of 26 researchers in IT and NL) report an analysis of a GRB
of 28 February 1997 (GRB970228). The major discovery is that of
an associated x-ray afterglow which fades within a few days
according to a power-law decay function (empirical). The authors
suggest that for the first time since the discovery of GRBs, it
will now be possible to correlate gamma-ray, x-ray, optical, and
radioastronomy observations. (Nature 19 Jun 97)
---------------------
AN HISTORIC MEETING DEVOTED TO GAMMA RAY BURSTS
Gamma ray bursts (GRBs) have been much in the news the past 10
months, principally because of correlative data from x-ray,
optical, and radio instruments. Last month saw the Fourth
Huntsville Symposium on Gamma Ray Bursts (15-20 Sep 1997,
Huntsville AL US), and the meeting is being called "historic".
There is apparently now a consensus that GRBs are cosmological
rather than galactic in origin, in other words from outside our
Milky Way galaxy. So that part of the 30-year puzzle concerning
GRBs is evidently solved. The other part of the puzzle concerns
the physical events producing the bursts, and for that part of
the puzzle there is apparently no consensus yet. It has recently
been proposed that GRBs are associated with the cataclysmic end
of massive stars, and if this is true, it is believed the
appearance of GRBs should provide data concerning the rate of
formation of such stars, a critical parameter that has evidently
been established by observation. In any case, the gamma ray burst
field has apparently now shifted to data analysis at new
wavelengths of the electromagnetic spectrum, with the emphasis
now on x-ray, optical, and radio observations from several
instrument sources, including the valuable BeppoSAX satellite,
the Hubble Space Telescope, and the Burst and Transient Source
Experiment (BATSE) aboard the Compton Gamma Ray Observatory. QY:
Bohdan Paczynski (Nature 9 Oct 97)
6. SEMICONDUCTOR-POLYMER INTERFACE TUNABLE DIODE
In physics, the term "tuning" refers to an adjustment of the
response (for example, oscillatory behavior) of a system to an
applied force by changing one or more of the system parameters.
In general, a diode is any two-electrode electrical system, and a
tunable diode is any such system whose voltage-current relation
(force-response characteristic) can be quantitatively tuned by
parameter variation. In physics, the term "work function" is the
minimum energy required to release an electron as it passes
through the surface of a conductor or semiconductor. A conjugated
polymer is a polymer with alternating double and single bonds in
its structure, the conjugation often producing enough electron
delocalization to make the polymer a conductor of electricity.
The term "doping" refers to the incorporation of impurities in a
substance to alter its physical properties. M. Lonergan (Univ. of
Oregon, US) reports experimental observations and analysis of a
tunable diode based on a hybrid inorganic-organic n-indium
phosphide/poly-(pyrrole)/nonaqueous electrolyte architecture.
Electrochemical manipulation of the work function of the conjug-
ated poly(pyrrole) enables continuous and active tuning of the
diode through a range from 0.0 to 0.6 volts. The author suggests
this type of tunable diode represents a new type of device archi-
tecture that allows the electrochemical control available with
doped conjugated polymers, and that a general path to diodes with
specific properties for specialized applications is now open. QY:
Mark C. Lonergan, Univ. of Oregon, Dept. of Chemistry 541-346-
4789 (Science 19 Dec 97)
7. LOCALIZATION OF LIGHT IN A DISORDERED MEDIUM
In physics, localization generally refers to the state of motion
of an entity being constrained to a region of dimensions smaller
than the material in which the entity exists. Anderson localizat-
ion, named after P.W. Anderson, who first discussed in 1958 the
absence of diffusion in certain random lattices, is essentially a
disorder-induced phase transition from a classical diffusion
regime to one in which the material behaves as a barrier or
perfect reflector. In the case of electrons, for example, the
phase transition is that from a conductor to an insulator. How
and when localization occurs depends on the nature of the part-
icle in motion and the nature of the medium. In the case of
electrons, the effect can be produced by interference of elec-
trons that have undergone multiple scattering by defects in a
solid. Wiersma et al (4 authors at 2 installations, IT NL) now
report direct experimental evidence for Anderson localization of
light in optical experiments involving strongly scattering semi-
conductor powders. The authors suggest that systems involving the
interaction with light with strongly disordered media may be
useful in the study of Anderson localization. Physicists are
apparently excited about these new experiments, suggesting they
are important for the impending new age of photonics that is
expected in the near future to take over from conventional
electronics. QY: Diederik S. Wiersma
(Nature 18/25 Dec 97)
8. QUANTUM-CONFINED STARK EFFECT IN CRYSTALLITE QUANTUM DOTS
When a particle is confined to a domain whose dimensions are of
the order of the wavelength of the particle, the states of motion
of the particle become quantized according to the laws of quantum
mechanics. This is the idea of the quantum well, which is essent-
ially a one-dimensional confinement domain, and a quantum dot is
essentially a zero-dimensional confinement domain. The physical
behavior of such quantum confinement domains exhibits new and
interesting effects that not only test fundamental theories, but
also offers possibilities for important technological applicat-
ions. In general, the Stark effect is an electric field effect in
which an applied electric field causes splitting of the spectral
lines of an atom into several lines of approximately the same
frequency. (When the applied field is a magnetic field, a similar
phenomenon occurs, and this is the Zeeman effect.) A crystallite
is a small and rudimentary form of crystal of undefined composit-
ion and which does not polarize light, and a nanocrystallite is
simply a crystallite of nanoscale dimensions (i.e., about 1 to
100 nanometers). What is interesting and important about nano-
scale domains is that they can be within the dimensional require-
ments for quantization of the states of motion of particles.
Empedocles and Bawendi (Massachusetts Inst. of Technology, US)
report a study of the quantum-confined Stark effect in single
cadmium selenide nanocrystallite quantum dots. The electric field
dependence of the single dot spectrum is characterized by a
highly polarizable excited state in the presence of randomly
oriented and time dependent local electric fields. The authors
suggest the observed behavior implies a potential use of this
system in electro-optic modulation devices. QY: M.G. Bawendi,
Mass. Inst. of Technology, Dept. of Chemistry 617-253-1845
(Science 19 Dec 97)
-------------------
Related Background:
REVERSIBLE METALLIC STATE TUNING OF QUANTUM DOT MONOLAYERS
Quantum dots ... behave as approximate single atomic entities,
and during the past decade there has been much interest in such
geometrically constrained systems because some of them exhibit
new properties of potentially great practical importance. One
method of studying these systems is in a so-called Langmuir
monolayer, named after the physical chemist Irving Langmuir
(1881-1957), who is considered responsible for perfecting the
monolayer technique. Now C. P. Collier et al (University of
California Berkeley, US; University of California Los Angeles,
US) have studied Langmuir monolayers of organically complexed
silver quantum dots in a system in which the dot separation can
be easily and quantitatively controlled by monolayer compression.
As the distance between metal surfaces in decreased from 1.2
nanometers to 0.5 nanometers, both quantum and classical effects
are observed in the optical signals of reflectivity and absorb-
ance. Essentially, what happens is that when the distance between
the quantum dots is reduced to less than 0.5 nanometers, the
electron distribution functions of the individual nanocrystals
overlap, producing electron delocalization, and the properties of
the monolayer suddenly switch from those of an insulator to those
of a metal. The transition is reversible, the insulator propert-
ies being restored when the monolayer is allowed to expand so
that the interdot distance becomes greater than 0.5 nanometers.
The authors suggest these results imply the possibility of
fabricating a new class of solids in which the electronic band
structure of the solid can be controlled by adjusting the
electronic wave function overlap between adjacent quantum dots.
QY: J. R. Heath, Univ. California Los Angeles, Chem.-Biochem.
(310) 825-3150 (Science 26 Sep 97)
9. A METHOD FOR PATTERNING OF ORIENTATED MESOSCOPIC DOMAINS
Nanotubules (not to be confused with carbon nanotubes) are simply
tubular arrangements of molecules on a nanoscale level, in other
words of dimensions of the order of nanometers. A substance is
said to be "mesoporous" if it has pores of dimensions in the
nanoscale range, and a "mesoscopic" domain, which literally means
a domain of dimensions between microscopic and macroscopic, is
the term usually applied to a domain of nanoscale dimensions.
Electro-osmosis is the movement of a liquid, in response to an
applied electric field, with respect to a fixed surrounding phase
such as a solid, the effect produced by intrinsic charge differ-
ences between the two phases. Capillary electro-osmosis is simply
the same effect occurring when the solid phase is a capillary
tube and the liquid phase fills the lumen of the tube. Trau et al
(6 authors at 2 installations, US) describe a method for the
directed growth of nanotubules involving fluid infiltration and
capillary electro-osmotic flow produced by an applied electric
field. The method allows the formation of orientated mesoporous
channels on a non-conducting substrate with an arbitrary micro-
scopic pattern. The authors suggest their technique provides a
convenient and economic method for fabrication of patterned
nanostructured materials for sensors, actuators, and optoelec-
tronic devices. QY: I.A. Aksay (Nature
18/25 Dec 97)
-------------------
Related Background:
NANOTUBULES MOLECULAR FILTRATION MEMBRANES
Because there is considerable interest in constructing membranes
with homogenous nanoscale pores for the purpose of separating
molecular species, there is a flourishing technology in the
production of such membranes. Now Kshama B. Jirage et al (3
authors at Colorado State University, US) report the use of
polymeric membranes containing a collection of monodisperse gold
nanotubules with inside diameters less than 1 nanometer in a
membrane-permeation experiment to achieve separation of small
molecules based on molecular size. The authors suggest that gold
nanotubule membranes, which have already been shown to have
charge-based transport selectivity, have now been shown to have
molecular size selectivity, and offer promise for the development
of highly selective membranes for chemical separations. QY:
Charles R. Martin
(Science 24 Oct 97)
10. ANALYSIS OF MONOLAYER FILM CATALYSIS
Substances that exhibit both hydrophilic (affinity for water) and
hydrophobic (affinity for nonaqueous liquids) properties in the
same molecule are called amphipathic, and when the molecular
architecture of amphipathic molecules is such that hydrophilic
and hydrophobic groups are at different ends of a more or less
linear molecule, the molecules of the substance will exhibit
certain special self-organizing properties when they are introd-
uced into an aqueous or nonaqueous liquid phase. In water, for
example, such molecules can form a monomolecular layer at the
surface, with the hydrophilic ends of the molecules interacting
with water, and the hydrophobic ends of the molecules in the
overlying air phase (essentially interacting with themselves).
Irving Langmuir (1881-1957) was the first to make a systematic
study of such interfacial monolayers, and he received the Nobel
Prize in Chemistry in 1932 for his work. Such monolayers can be
treated as two-dimensional phases exhibiting solid, liquid, and
gaseous states, and when compressed to a solid state by appropr-
iate use of mechanical boundaries, it is possible to transfer the
organized layers to a dipped solid surface, forming what are
known as Langmuir-Blodgett films. One can then use these films on
solid surfaces to examine the chemical properties of particular
substances organized in one or more organized molecular layers.
Tollner et al (4 authors at Weizmann Inst., Rehovoth IL) report
the use of catalytically active Langmuir-Blodgett films of a
rhodium complex to determine the effect of the molecular order of
metal complexes on catalytic activity. They found the complex
showed low catalytic activity in solution, but high catalytic
activity in the film, with the film activity highly dependent on
orientation of the complex. The authors suggest the observed rate
dependence on temperature strongly implicates the molecular order
of a metal complex as an important dimension in catalysis. QY:
David Milstein (Science 19 Dec
97)
(continued in Part 2)
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
SCIENCE-WEEK - Part 2
A Free Weekly Digest of the News of Science
January 9, 1998
----------------------------------------------------------------
Contents of Part 2:
11. Synthesis of Multidimensional Large-Cage Zeolite Structures
12. Selection of Broad-Scope Enzymes by Antibody Catalysis
13. Analysis of Intracellular Signaling Mechanisms
14. Abscisic Acid Signaling in Plants
15. Evidence for Cyclic AMP Signaling in Higher Plants
16. Transgenic Sheep Expressing Human Clotting Factor Protein
17. More Evidence that Prion Protein Binds Copper In Vivo
18. Involvement of Immune System B-Cells in a Prion Disease
19. Regeneration of Axons in Central Nervous System White Matter
20. Animal Models of HIV-1 Disease
-----------------------------------------------------------------
11. SYNTHESIS OF MULTIDIMENSIONAL LARGE-CAGE ZEOLITE STRUCTURES
Zeolites are members of a group of hydrated aluminosilicate
minerals occurring in the cavities of igneous rocks (rocks
produced by solidification from a molten state; for example,
granite) and various volcanogenic sediments. They are also
manufactured for their ion exchange properties (the exchange of
zeolite ions with solute ions) and selective adsorption
properties (specific adsorption of solutes). They have an open
crystal structure and can also be used as molecular sieves for
partitioning and sequestration of solutes according to the
dimensions of the zeolite pores and the dimensions of the solute
molecules. Bu et al (3 authors at Univ. of California Santa
Barbara, US) report the synthesis of zeolite-type structures with
large cages interconnected by multidimensional 12-ring channels,
with more than a dozen large-pore materials prepared with 3
different topologies involving various metals at the tetrahedral
coordination sites (aluminum (or gallium), cobalt (or manganese,
magnesium, or zinc), and phosphorus). The authors suggest their
results indicate there might exist a large family of zeolite type
structures not yet synthesized, and that some of these unknown
phases may be accessible with their approach. QY: Xianhui Bu,
Univ. of Calif. Santa Barbara, Dept. of Chemistry 805-893-2638
(Science 19 Dec 97)
12. SELECTION OF BROAD-SCOPE ENZYMES BY ANTIBODY CATALYSIS
An antibody is a protein molecule produced by vertebrates that
binds with high specificity to a foreign entity (antigen) that
has entered the system by one means or another (for example, via
bacteria, tissue grafts, or blood transfusions). Antibodies are
therefore key elements in all vertebrate immune systems. That is
the first point. The second point is that we now know that
enzymes work the way they do mostly because they bind transition
state entities in chemical reactions, this binding lowering the
energy barrier to the transition state, and thereby increasing
the reaction rate many-fold. Which provokes the notion that it
might somehow be possible to use the high specificity of anti-
bodies in catalysis. And the notion is correct. A catalytic anti-
body, sometimes called an "abzyme", is an antibody capable of
catalyzing specific chemical reactions. "Reactive immunization"
is a new term to describe a synthetic antibody specificity that
involves a covalent chemical reaction with an antigen rather than
weaker affinity bonds, and new antigens specifically synthesized
or selected for this reactive process are called "reactive
immunogens". In biological systems, glycolysis (also known as
Embden-Meyerhof pathway), involving the breakdown of glucose, is
one of the main energy producing pathways in the cell, and
anaerobic glycolysis is glycolysis in the absence of oxygen.
Decarboxylation is the removal of CO(2) from organic compounds,
and in biological systems often involves the conversion of amino
acids to amines. Lysine is one of the amino acids found in
biological systems. Barbas et al (11 authors at Scripps Res.
Inst., US) report the preparation of catalytic antibodies by
reactive immunization, the process yielding aldolase catalytic
antibodies that approximate the rate acceleration of the natural
enzyme used in glycolysis. But unlike the natural enzyme, the
antibody aldolases catalyze a variety of aldol reactions and
decarboxylations. Crystal structure analysis of one of the
antibodies identified the lysine residue selected in the
immunization process, and the lysine residue is apparently deeply
buried in a hydrophobic pocket at the base of the binding site.
The authors suggest that an early defining event in the evolution
of some natural enzymes was an interaction with reactive
materials such as toxins in a process similar to the induction of
catalytic antibodies with a reactive immunogen. QY: Richard A.
Lerner, Scripps Research Institute 619-784-1000
(Science 19 Dec 97)
13. ANALYSIS OF INTRACELLULAR SIGNALING MECHANISMS
In multicellular organisms, chemical messengers of various types
are important entities in the communication between cells
necessary for the function and viability of cells, tissues, and
the organism itself. These messengers usually interact with the
surfaces of cells, particularly with specific receptors on cell
surfaces. Such an interaction is called an "extracellular
signal", and what happens next is a cascade of internal signal
events that effectively transmit the external signal from the
cell membrane to one or more places inside the cell, especially
to the cell nucleus. This sequence in internal signal events
apparently involves specific protein-protein and protein-
phospholipid interactions, with the interactions mediated by
protein domains (regions) of tertiary structure (higher order
configuration) that have evidently been conserved through
evolution. The details of these biochemical interactions are
becoming apparent, at least in some types of somatic cells, so
that molecular biologists are now characterizing the involved
proteins as anchoring (docking) proteins, adaptor proteins,
scaffold proteins, and so on, according to the role played by the
particular protein in the spatial location and translocation and
signal events that eventually produce important reactive or
regulatory responses of the cell. Pawson and Scott (2 installat-
ions, CA US), in a review of how extracellular signals are
relayed from the plasma membrane to specific intracellular sites,
discuss the role of scaffold, anchoring, and adaptor proteins
that contribute to signal transduction by recruiting active
enzymes into signaling networks or by placing enzymes close to
their substrates. The authors suggest that the challenge ahead is
to understand both the physiological functions and regulation of
such signaling networks. QY: Tony Pawson, S. Lunenfeld Res.
Inst., Mt. Sinai Hospital, Toronto, ON M5G 1X5 CA
(Science 19 Dec 97)
14. ABSCISIC ACID SIGNALING IN PLANTS
Abscisic acid is a plant hormone synthesized in wilting leaves
and opposing the effects of most other plant hormones by
inhibiting cell growth and division, seed germination, budding,
etc. It also induces dormancy of the plant, and participates in
the opening and closing of the leaf stomata (pores in the leaf
through which CO(2) enters and water exits). Adenosine diphosph-
ate (ADP) is involved in the cellular metabolism of adenosine
triphosphate (ATP), an important "high-energy" compound, and
cyclic-ADP-ribose is a complex of a cyclic form of ADP with a
ribose sugar. In general, the "second messenger" is an intermed-
iary compound that couples extracellular signals to intracellular
processes with amplification of the transduced signal. Phosphor-
ylation is the addition of a phosphate group to an organic
compound, and is the most important energy transfer process in
biological metabolism. Wu et al (7 authors at 2 installations,
US) report single-cell microinjection experiments in tomato plant
to identify possible abscisic acid signal transduction intermed-
iates. Cyclic-ADP-ribose was identified as a signaling molecule,
and its effects are apparently mediated by calcium ions. The
authors suggest that cyclic-ADP-ribose is a second messenger
responsible for initiating the cascade of Ca(++) increases and
subsequent Ca(++) dependent phosphorylation and dephosphorylation
during abscisic acid signal transduction.
QY: Nam-Hai Chua
(Science 19 Dec 97)
15. EVIDENCE FOR CYCLIC AMP SIGNALING IN HIGHER PLANTS
Complementary DNA (denoted as cDNA) is a single-stranded
complementary DNA copied from messenger RNA (mRNA) by the enzyme
reverse transcriptase. A protoplast is a plant cell as it exists
inside the rigid cell wall, or in some cases as it exists free of
the cell wall. One of the reaction products of ATP is cAMP
(cyclic AMP, or adenosine 3,5-monophosphate), which acts as an
intracellular hormone (i.e., a chemical messenger). Cyclic AMP is
derived from ATP in a reaction catalyzed by the enzyme adenylyl
cyclase (also called adenyl cyclase and adenylate cyclase), and
in animal cells cyclic AMP is often a second messenger. Auxins
are plant growth substances (hormones) involved in many varied
aspects of plant growth, and forskolin is a diterpene that
apparently activates various isoforms of adenylyl cyclase.
Ichikawa et al (7 authors at Max Planck Inst. fur Zuchtungs-
forschung, Koln DE) now report the isolation of a complimentary
DNA encoding adenylyl cyclase from a tobacco plant cell line,
apparently the first from a higher plant. They also report that
tobacco protoplasts treated with cAMP or forskolin no longer
require auxin to divide, and that an adenylyl cyclase inhibitor
inhibits cell proliferation in the presence of auxin. The authors
suggest that cAMP is involved in auxin-triggered cell division in
higher plants. QY: Richard Walden
(Nature 18/25 Dec 97)
16. TRANSGENIC SHEEP EXPRESSING HUMAN CLOTTING FACTOR PROTEIN
A transgenic animal is an animal into which genetic material from
another organism has been transferred, the transferred and
incorporated new animal genes then being expressed with the
resultant production of specific proteins. Human clotting factor
IX, which is vitamin K dependent, is one of the blood plasma
factors involved in the series of events involved in blood
coagulation, and deficiency of factor IX is the genesis of human
hemophilia type B. The term "somatic cells" is a generic term for
all cell other then egg cells and sperm cells, and transfection
is the uptake of exogenous (foreign) DNA fragments in solution
directly into animals cells in laboratory culture, and is one
method of introducing foreign genes into cells. Nuclear transfer
is a technique involving the transfer of the nucleus of one cell
into another cell, and in the context of this report involves the
transfer of the nucleus of a transfected cell into egg cells that
have had their nuclei removed. Schnieke et al (9 authors at 2
installations, UK) report the production by means of nuclear
transfer of transgenic sheep expressing human clotting factor IX
in sheep milk. The authors suggest their results demonstrate that
somatic cells can be subjected to genetic manipulation in vitro
and produce viable animals by nuclear transfer, with the product-
ion of transgenic sheep by nuclear transfer requiring fewer than
half the animals needed by previous methods (reported by this
group) involving microinjection of DNA into the nuclei of fertil-
ized egg cells. They further point out that their procedures for
transfection and growth from single-cell clones are essentially
the same as those required for gene targeting, and that the
realistic prospect of targeted genetic manipulation in a live-
stock species should open a vast range of new applications and
research possibilities. QY: Angelika E. Schnieke, PPL Therapeut-
ics, Roslin, Midlothian, EH25 9PP, Scotland, UK. (Science 19 Dec
97)
17. MORE EVIDENCE THAT PRION PROTEIN BINDS COPPER IN VIVO
Prions are a class of poorly understood proteins implicated in a
number of exotic human neurological diseases and in some common
animal diseases such as sheep scrapie and bovine spongiform
encephalopathy in cattle ("mad cow disease"). What is remarkable
about prions is that they behave as infectious agents, but they
are 100 times smaller than viruses and their mechanism of
replication is unclear. All the prion diseases are apparently
associated with the accumulation in the brain of an abnormal
protease-resistant isoform of the prion protein PrP. In other
words, an abnormal variant of the normal PrP is somehow copied or
produced by the disease process, which can be initiated by
introducing infectious prion into the system. A chelate is a
metal coordination complex in which one ligand coordinates at two
or more points to the same metal ion, and a glycine chelate is a
chelate involving the amino acid glycine. Brown et al (13 authors
at 4 installations, DE CA UK) report that the amino-terminal
domain of normal prion protein exhibits 5 to 6 sites that bind
copper presented as a glycine chelate, that genetically
engineered mice deprived of prion protein show severe copper
reductions in various cell membrane fractions and altered
electrophysiological responses to excess copper. The authors
suggest their findings indicate that normal prion protein can
exist in a copper-metalloprotein form in vivo, and that like
other cuproproteins implicated in the pathogenesis of neurolog-
ical disease, prion proteins may regulate copper distribution.
QY: Hans Kretschmer
(Nature 18/25 Dec 97)
-------------------
Related Background:
AN APPARENT INVOLVEMENT OF PRION PROTEIN IN COPPER BINDING
Copper is essential as a trace metal for the function of certain
enzymes and other biomolecules, but even a moderate excess can be
highly toxic in certain tissues. ... At a recent meeting of the
Society for Neuroscience (24-30 Oct New Orleans, US) David Brown
(Univ. of Cambridge, UK) reported that normal prion protein
apparently binds copper ions and thus protects neurons against
the cytotoxic effects of the metal. He suggests the transformed
disease-causing prion protein might not be able to perform this
important function. But this idea is not without problems, since
there is evidence that in genetically engineered mice without
normal prion protein there is no resulting pathology -- which in
turn suggests it is the transformed protein that is directly
pathogenic. (Science 21 Nov 97)
18. INVOLVEMENT OF IMMUNE SYSTEM B-CELLS IN A PRION DISEASE
Lymphocytes are a type of leukocyte (white blood cell)
responsible for the immune response. There are two classes of
lymphocytes: 1) the B-cells, which when presented with a foreign
chemical entity (antigen), change into antibody producing plasma
cells; and, 2) the T-cells, which interact directly with foreign
invaders such as bacteria and viruses. Klein et al (10 authors at
2 installations, CH) now report that in genetically engineered
immune-deficient mice, all mutations that disrupt the different-
iation and response of B-lymphocytes prevent the development of
clinical scrapie. The authors suggest the possibility that B-
cells may be the physical carriers of prions might require a re-
evaluation of the safety of blood products, and that in prion-
infected individuals, systemic suppression of B-cells may
mitigate the course of spongiform encephalopathies. QY: Adriano
Aguzzi
(Nature 18/25 Dec 97)
-------------------
Related Background:
USE OF MONOCLONAL ANTIBODY TO DISTINGUISH PRION ENTITIES
A monoclonal antibody is essentially a biosensor device
constructed in the laboratory from living cells. The procedure
involves fusing a specific antibody-producing immune system
B-cell with an immortal cancer cell, so that the resultant cell
type is now an immortal antibody-producing cell that replicates
itself in vitro to produce a large number of antibodies that can
be used to detect the specific antigen. ... Korth et al (17
authors at 8 installations, CH) now describe a monoclonal
antibody (15B3) that can discriminate between the normal and
disease-specific forms of the prion protein (PrP). The authors
suggest this long sought-after entity should be invaluable for
characterizing the infectious particle and for diagnosis of the
transmissible spongiform encephalopathies such as bovine spongi-
form encephalopathy and Creutzfeldt-Jakob disease. QY: C. Korth
(Nature 6 Nov 97)
19. REGENERATION OF AXONS IN CENTRAL NERVOUS SYSTEM WHITE MATTER
When examining the gross anatomy of the mammalian brain and
spinal cord, a striking feature is the presence of large regions
with an opalescent ivory color. The color is due to myelin, the
substance that sheaths many nerve fibers in the central nervous
system. In the vertebrate central nervous system, the axons of
nerve cells involved in physiological functions that require
rapid signaling (for example, the neural control of voluntary
muscle) are wrapped in myelin with a special consequence. The
myelin sheath consists of concentric layers of electrically
insulating lipid material, but the sheath is periodically
interrupted, and at the points where the sheath is interrupted so
is the electrical insulation interrupted. The result, predictable
from the classical physics of electrical transmission lines and
the electrical parameters of nerve fibers, is that the propagat-
ion of an electrical pulse along such nerve fibers occurs at a
velocity much higher than that found in unmyelinated fibers.
Glial cells are cells of the central and peripheral nervous
system that metabolically support neurons and produce the
multiple membrane layers called myelin and enfold nerve cell
axons with it. The glial cells are found everywhere in the brain
and spinal cord, and one result of a localized injury to the
central nervous system is a local proliferation of glial cells to
form a scar matrix. Concerning brain and spinal cord injury, it
has always been a canon of neurobiology that adult central
nervous system neurons cannot regenerate after injury to re-
establish the connections to other cells necessary for proper
functioning. Davies et al (6 authors at 2 installations, US UK),
using microtransplantation techniques, now report that adult
central nervous system white matter can support long-distance
regeneration of adult axons provided the reactive glial
extracellular matrix at the site of the lesion can be bypassed.
The authors suggest this is the first time this glial barrier to
axon regeneration has been noted.
QY: Jerry Silver (Nature 18/25 Dec 97)
20. 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
(Science 19 Dec 97)
---------------------------------------------
BOOK NOTES
J. Gerhart and M. Kirschner: CELLS, EMBRYOS, AND EVOLUTION
Toward a Cellular and Developmental Understanding of Phenotypic
Variation and Evolutionary Adaptation.
Blackwell, 1997, 655p, US50
An undergraduate text ranging from paleontology to the cell and
developmental biology of modern organisms. The two authors are
noted molecular and cellular biologists.
S. Clark: TOWARDS THE EDGE OF THE UNIVERSE
A Review of Modern Cosmology
Wiley, 1997, 232p, US44.95
An introductory overview with worked examples of relevant
calculations in cosmology. The formation of galaxies, the fate of
the universe, the Big Bang, instrumentation and methods, etc.
Alex Gringauz: INTRODUCTION TO MEDICINAL CHEMISTRY
How Drugs Act and Why
Wiley, 1997, 736p, US89.95
Designed to bridge the gaps between organic chemistry,
biochemistry, and biology. A comprehensive integration of the
chemical and physiological aspects of drugs. Organized by
therapeutic topics covering the major areas of pharmaceutical
research.
Bernard V. Liengme:
A GUIDE TO MICROSOFT EXCEL FOR SCIENTISTS AND ENGINEERS
Wiley, 1997, 224, US39.95
An introduction to the technical functions of the program,
particularly those used for analyzing and presenting experimental
results. Introduction to spreadsheets, formulas, charts, curve-
fitting, equation-solving, macros, statistical functions, logic
functions, differentiation, integration, etc.
Linda Reichl: A MODERN COURSE IN STATISTICAL PHYSICS
Wiley, 1998, 832p, US84.95
Thermodynamics of phase transitions, elementary probability
theory, limit theorems, stochastic dynamics, Brownian motion,
order-disorder transitions, renormalization theory, interacting
fluids, hydrodynamic processes near equilibrium, transport
theory.
Harriet Ritvo:
THE PLAYTPUS AND THE MERMAID AND OTHER FIGMENTS OF THE
CLASSIFYING IMAGINATION
Harvard Univ., 1997, 288p, US29.95
A study of 18th and 19th century British taxonomic practices. A
readable collection of entertaining vignettes revealing the
attitudes, prejudices, and mild insanities of the Victorian and
pre-Victorian eras.
V. Szebehely and H. Mark: ADVENTURES IN CELESTIAL MECHANICS
An exploration of revolutionary ideas in astronomy from Kepler
and Newton to the theoreticians of the 20th century. Discovery,
evolution, and behavior of the universe; circular, elliptic,
hyperbolic and parabolic orbits; development of the calendar;
Newton's laws of dynamics and gravity; recent breakthroughs in
artificial satellite and spacecraft technology.
Vladimir I. Vernadsky: THE BIOSPHERE
Complete Annotated Edition
Copernicus, 1997, 250p, US30
The classic 1926 monograph by the mineralogist and biogeologist
who originated the concept of the biosphere as it is studied
today. This is apparently the first complete unabridged English
translation from the Russian.
--------------------------------
|