ScienceWeek

SCIENCE-WEEK - Part 1/3

A Free Weekly Digest of the News of Science

February 6, 1998
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"Geological time inspires awe, and there are no
certainties about the future, but perhaps it is
almost certain that someday they will collect our
skulls and call us Early Man."

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Contents of This Issue:

Part 1:
1. Swiss Government to Preempt Gene Technology Referendum
2. More Controversy Concerning Policy on Xenotransplants
3. Apparent Extensive Plagiarism by Polish Scientist
4. Historical Evidence of Deception by Wireless Inventor Marconi
5. Mounting Evidence for a Sub-Surface Ocean on Jupiter's Europa
6. A Simulation Model for Modern and Glacial Climates
7. Evidence for a Quark-Gluon Plasma

Part 2:
8. A Method for the Synthesis of Durable Organic Gels
9. A Functional Non-Protein Model for an Enzyme Catalyst
10. Rho Enzymes and the Actin Cytoskeleton
11. Intermediate Filaments and Intracellular Scaffolding
12. Motor Proteins and Organelle Transport
13. On the Function of Unconventional Myosins
14. A Criticism of the Prion Hypothesis
15. A New Protein That Acts as an Embryological Head Inducer

Part 3:
16. On the Chemistry and Neurophysiological Action of Vanilloids
17. The Role of Visual Experience in Development of Visual Cortex
18. Phantom Sensations Evoked by Human Thalamic Microstimulation
19. An HIV Protein That Protects the Host Cell Against T-Cells
20. Evidence for Axonal Transection in Multiple Sclerosis Lesions

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1. SWISS GOVERNMENT TO PREEMPT GENE TECHNOLOGY REFERENDUM
The Swiss government is attempting to preempt the June 1998
referendum on a constitutional provision that would impose major
restrictions on genetic engineering and the use of transgenic
animals. The proposed constitutional provision, put into process
in 1992, is supported by environmental and animal rights groups
but opposed by the majority of Swiss scientists and apparently
also by the majority of the public. The government, however, is
evidently taking no chances, viewing passage of the referendum as
a potential catastrophe that may ruin Swiss biomedical research
and the huge Swiss pharmaceutical industry. The government plans
to initiate legislative measures that would provide for strict
controls without banning what is deemed to be ethical and
necessary research. (Nature 22 Jan 98)

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Related Background:

ANOTHER VIEW OF THE SWISS GENE TECHNOLOGY REFERENDUM
F. Cavalli (Ospidale San Giovanni Bellinzona, CH), a member of
the Swiss Parliament, in a letter to the journal Science,
responds to the recent editorial by Nobel Laureate Rolf M.
Zinkernagel concerning the coming Swiss referendum on a
constitutional prohibition of gene manipulation. Cavalli suggests
that Zinkernagel and others have made an erroneous assessment of
the current situation in Switzerland, and that there is distrust
throughout Europe "of giant companies whose solicitude for their
shareholders appears to outweigh their concern for their
thousands of workers."QY: Franco Cavalli, Ospidale San Giovanni,
6500 Bellinzona, CH (Science 9 Jan 98)

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ON THE SWISS CONSTITUTIONAL PROHIBITION OF GENE MANIPULATION
There is an interesting science policy development brewing in
Switzerland. A policy formulation called the Gene Protection
Initiative has come into existence, and it will be voted on in a
national referendum in 1998. This initiative, if approved by the
public referendum, will result in a constitutional prohibition of
gene manipulation, prohibition of the use and patenting of gene-
modified animals (including worms and flies), and prohibition of
the cultivation of gene-modified plants. The Swiss scientific
community says that if the referendum is passed it will cause the
end of Swiss biotechnology and molecular biology. Both houses of
the Swiss parliament have voted against the Initiative, agreeing
with the scientists and the Swiss industrial biotechnology
community that passing the referendum will produce a disaster. At
the present time it is not clear how the public will vote. Those
supporting the initiative claim that gene-modified plants cause
allergies, that science is one step away from the creation of
super-monsters, that scientists lack ethics, morals, and a sense
of responsibility, and that scientists have let the public down
on too many occasions. So they say gene technology must be banned
from Switzerland, and they hope the rest of the world will follow
suit. In an editorial in the journal Science, Rolf M. Zinkernagel
(Institute for Experimental Immunology, Univ. of Zurich, CH) is
optimistic that the good sense of the Swiss public will prevail
and that the Gene Protection Initiative will be defeated in the
referendum, but he points out that scientists must play their
part in dispelling the negative image of science and scientists,
and they must educate the public concerning the beneficial
applications of modern science. (Science 14 Nov 97)

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MOVEMENTS IN UK AND EU TO BAN TRANSGENIC ANIMAL RESEARCH
There are movements underway in Britain and Europe to ban or
rigidly control the use of transgenic animals in biological
research. In the UK there are calls for a commission of inquiry
to investigate the welfare of transgenic animals. A recent survey
supported by the European Commission into public attitudes to
biotechnology evidently showed most respondents in EU countries
consider the creation of transgenic animals for research and for
organ transplantation to be morally unacceptable. In Switzerland,
Swiss scientists have issued a warning that biomedical research
in universities will be seriously harmed if a referendum to be
held next year to restrict genetic engineering (including a ban
on the use of transgenic animals) wins approval. An irony is that
surveys in Switzerland have shown that although three-quarters of
the population is against field trials of genetically modified
organisms, novel food, and cloning, a majority are in favor of
medical applications of technology. The apparent view of most
biologists about this matter is not complicated. The feeling
among biologists is that after centuries of arduous struggle by
thousands of biological researchers to understand fundamental
principles and apply them in medicine to alleviate suffering and
extend life, we are now, at the end of the 20th century, at the
threshold of the most important applications of basic biological
science to human health and the control of human disease. Genetic
engineering and the use of transgenic animals are absolutely
essential to extend molecular biology and apply it expeditiously
to human clinical medicine. It is indeed ironic that the same
people who call for a halt to transgenic animal research expect
the ultimate in scientific expertise when they or their children
are victims of disease or other biological misfortunes. It is sad
to have a public uneducated about these matters; it is even
sadder that many politicians deem it wisdom to follow the public
mood rather than lead it. (Nature 24 Jul 97)


2. 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  (Nature 22 Jan 98)

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

Related Background:

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 
(Nature 16 Oct 1997)

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XENOTRANSPLANTATION CONFLICT BETWEEN SURGEONS AND VIROLOGISTS
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. 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 1997)


3. APPARENT EXTENSIVE PLAGIARISM BY POLISH SCIENTIST
A case of intensive plagiarism by a Polish scientist has
apparently been uncovered by the use computerized literature
searches. It seems that Andrzej Jendryczko, a chemical engineer
and former professor at the Medical University of Silesia
(Katowice, PL), published with a dozen co-authors at least 30
biomedical research papers repeating verbatim passages from other
authors without giving credit. Five of the co-authors are full
professors or heads of university departments. In one year,
apparently, Jendryczko, who is not an MD, published 2 papers
reporting data from 300 patients and 1000 patients, all of it
with no credit to the data sources. Marek Wronski, an oncologist
at the Staten Island University Hospital New York (US) uncovered
the evidence of the various plagiarisms, including a paper
published in the Zentralblatt fur Gynakologie 1991 under the
names of A. Jendryczko and M. Drozdz that is virtually identical
to a paper published in 1979 in the Journal of Maxillofacial
Surgery by 3 different authors. Jendryczko is apparently
maintaining his innocence. Although a number of Polish colleagues
have evidently denounced him, Jendryczko was recently appointed a
professor at the Polytechnic Institute of Czestochowa.
(Science 23 Jan 98)


4. HISTORICAL EVIDENCE OF DECEPTION BY WIRELESS INVENTOR MARCONI
Guglielmo Marconi (1874-1937) is given credit for the invention
of wireless telegraphy (and the birth of radio), and in 1909 he
shared the Nobel Prize in Physics with Karl Braun (who, among
other things, invented the crystal rectifier) for that work.
Marconi's invention of wireless telegraphy combined the use of
the Hertz method of producing radio waves and a receiving device
called a "coherer" for detecting the waves. A coherer is
essentially an enclosure containing a granular conductor (e.g.,
metal filings) between two electrodes, the enclosure becoming
highly conducting when subjected to an electric field. Since
amplification was not available in the early days of wireless
telegraphy, the sensitivity of the receiving device was of
paramount importance in the utilization of the invention over
long distances. Marconi's first experiments were made over short
distances beginning in 1895, apparently using a coherer invented
by Eduoard Branly (FR). This coherer was not adequate for long
transmissions and weak signals, and Marconi evidently did not
reveal the later coherers he used, especially the device used to
receive the first trans-Atlantic wireless signal in 1901. It now
appears the coherer used in that famous transmission was invented
and published from Calcutta in the British Proceedings of the
Royal Society 1899 by biologist and physicist Jagadis Chandra
Bose (IN), who was never mentioned later by the Europeans, never
acknowledged by Marconi, and who probably ought to have shared
the Nobel Prize in Physics with Marconi and Braun in 1909. Bose,
who apparently never protested his exclusion from credit, is
portrayed as "uninterested in the commercialization of scientific
inventions". Marconi expended great energy commercializing his
invention, played a role in the Italian government in World War
I, supported the Italian Fascist movement and government in the
1920s and 1930s, and was buried with honors by Mussolini. The
story of Bose's role in wireless telegraphy was recently reported
in the Proceedings of the IEEE by Probir Bondyopadhyay.
(Science 23 Jan 98)


5. MOUNTING EVIDENCE FOR A SUB-SURFACE OCEAN ON JUPITER'S EUROPA
Europa is the smallest of Jupiter's so-called Galilean
satellites, with a diameter 3138 kilometers. It has a smooth
crust of water-ice, criss-crossed by a network of light and dark
linear markings. It has been thought that beneath the crust there
may be an ocean of water, and a variety of ice tectonics has been
proposed to be operating on the surface. The Galileo spacecraft
is a US National Aeronautics and Space Administration mission to
Jupiter launched in 1989. ... ... Now Carr et al (22 authors at
12 installations, US DE) report high-resolution (54 meters per
pixel) Galileo spacecraft images of Europa that provide evidence
for mobile "icebergs", the detailed morphology of the terrain
strongly supporting the presence of liquid water at shallow
depths below the surface either at present or at some time in the
past. In a contiguous report, Pappalardo et al (11 authors at 7
installations, US) report an analysis of certain surface features
of Europa also revealed by high-resolution images from the same
spacecraft, and conclude the features are surface manifestations
of localized relatively warm ice masses that have risen through
the subsurface, and are consistent with a subsurface liquid water
ocean. Results from 2 other contiguous reports are also
interpreted as consistent with the idea of a subsurface liquid
water ocean on Europa.
QY: Michael H. Carr ; R.T. Pappalardo
; Robert Sullivan
 (Nature 22 Jan 98)

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

Related Background:

NEW DETERMINATIONS OF INTERNAL STRUCTURE OF JUPITER'S MOON EUROPA
Data from the December 19, 1996 Galileo spacecraft encounter
with the Jovian moon Europa have now been published, and the
consensus is that Europa has a water ice-liquid outer shell
about 100 to 200 kilometers thick. Gravitational effects on the
spacecraft are consistent with two models of Europa. In one the
core is a mixture of rock and metal, and in the other it is
purely metallic. Further data concerning Europa's intrinsic
magnetic field is needed to distinguish between the two models.
Reports were provided by J. D. Anderson et al (California
Institute of Technology, Pasadena CA US; University of
California Los Angeles, CA US) and M. G. Kivelson et al
(University of California Los Angeles, CA US; Imperial College of
London UK; California Institute of Technology, Pasadena CA US).
Science 23 May 97)

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POSSIBILITY OF A DEEP OCEAN ON JUPITER'S MOON EUROPA
Jupiter's satellite system consists of at least 16 moons, the
four largest of which are called the Galilean moons, since they
were discovered by Galileo. They are Io, Europa, Ganymede, and
Callisto, in order of their orbital distance from Jupiter.
Europa, which is slightly smaller than Earth's moon, has a thick
icy crust, and may also have a liquid water mantle beneath this
crust. Very few craters are present on Europa, which suggests an
active surface that renews itself and thus erases craters as fast
as they form from impacts. The surface also shows numerous lines
about 30 km wide and 1000 km long, and these have been interpr-
eted to be breaks in the crust where water from below has
refrozen. The possible existence of a liquid water mantle beneath
the ice on Europa is of great interest to planetary scientists,
since such a mantle might contain life forms. Until recently,
most planetary scientists apparently doubted any contemporary
existence of a liquid water mantle. But new analyses have been
appearing, and at the meeting last week of the Division for
Planetary Sciences of the American Astronomical Society in
Boston, a consensus appears to have formed that a water mantle
probably existed in the recent past, and may even exist today. In
December, the Galileo spacecraft, as part of its extended
mission, will take an even closer look at Europa, with the resol-
ution of its best images expected to improve from 70 meters to 10
meters, and planetary scientists are hopeful the question of the
state of water on Europa will be answered. (Science 8 Aug 97)


6. A SIMULATION MODEL FOR MODERN AND GLACIAL CLIMATES
In 1920, the meteorologist Milutin Milankovic proposed that small
changes in Earth's orbit, precession, and inclination affect the
heat balance and modify climate (the alterations called "solar
forcing"). The Milankovic hypothesis was not taken seriously
until 1976, when teams studying sediment cores from the ocean
floor constructed a history of ocean temperature that matched the
predictions of the Milankovic hypothesis, with two different
ocean cores providing similar results. Until now, simulation
models of Earth's climate history have been either ocean models
or atmosphere models, with no model accounting for the interact-
ions between the ocean and the atmosphere aside from adjustable
heat flux parameters that result in only a weak theory. In
general, complete solutions of these individual models have
involved prohibitive computation times. The term "glacial
maximum" refers to the time or position of the greatest extent of
glaciation, and the term "hydrologic cycle" refers to the
complete cycle through which water passes: from the ocean,
through the atmosphere, to the land, and back to the ocean.
... ... Ganopolski et al (4 authors at Potsdam Institute for
Climate Impact Research, DE) now report a moderately simplified
global coupled ocean-atmosphere model to simulate the equilibrium
climate of both the present and of the last glacial maximum, and
that the model successfully predicts the atmospheric and oceanic
circulations, temperature distribution, hydrologic cycle, and
sea-ice cover of both periods without using flux adjustments. The
authors suggest that changes in oceanic circulation, particularly
in the Atlantic Ocean, play an important role in glacial cooling,
and that ultimately the challenge is to produce a simulation of
glacial cycles driven only by the Milankovic cycles in solar
forcing. QY: Stefan Rahmstorf  (Nature
22 Jan 98)


7. EVIDENCE FOR A QUARK-GLUON PLASMA
The fundamental forces comprise the gravitational force, the
electromagnetic force, the nuclear strong force, and the nuclear
weak force. A quark is a hypothetical fundamental particle,
having charges whose magnitudes are one-third or two-thirds of
the electron charge, and from which the elementary particles may
in theory be constructed. Quarks are held together through the
exchange of gluons, massless particles that carry the strong
force. According to current theory, quarks and gluons cannot
exist in isolation. But theory also predicts that at temperatures
10^(12) degrees Kelvin or greater (such as existed during the
first 0.01 second of the history of the universe) a drastic
change in the structure of nuclear matter occurs, and only
descriptions in terms of quarks and gluons apply. A plasma is a
gas consisting entirely of equal numbers of positive and negative
charges. ... ... F. Wilczek (Institute for Advanced Study
Princeton, US), in a short review of recent experiments that for
the first time apparently produced a quark-gluon plasma, "an
extraordinary new state of matter", suggests that an important
question is whether, as a function of temperature, the transition
from ordinary matter to a quark-gluon plasma is continuous or
discontinuous. A discontinuous transition could imply explosive
instabilities, which in turn may have been important in the
evolution of the early universe.
QY: Frank Wilczek  (Nature 22 Jan 98)


(continued in Part 2)

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SCIENCE-WEEK - Part 2/3

A Free Weekly Digest of the News of Science

February 6, 1998

Contents of Part 2:

8. A Method for the Synthesis of Durable Organic Gels
9. A Functional Non-Protein Model for an Enzyme Catalyst
10. Rho Enzymes and the Actin Cytoskeleton
11. Intermediate Filaments and Intracellular Scaffolding
12. Motor Proteins and Organelle Transport
13. On the Function of Unconventional Myosins
14. A Criticism of the Prion Hypothesis
15. A New Protein That Acts as an Embryological Head Inducer

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

8. A METHOD FOR THE SYNTHESIS OF DURABLE ORGANIC GELS
In general, a gel is an easily deformable pseudo-solid (for
example, a jelly), and the formation of gels from new types of
liquids is always of interest to chemists since there are usually
possibilities for important applications in which a pseudo-solid
state of a component would be advantageous. Most gels, however,
are not stable, particularly at high temperatures.
... ... De Loos et al (5 authors at University of Groningen, NL)
now report the conversion of various organic solvents (e.g.,
cyclohexane, butyl acetate, benzene, 1,2-dichloroethane, etc.)
into ordered gels that remain stable at elevated temperatures and
for prolonged periods of time. The gels are said to be different
than other organic gels, first forming a network structure due to
hydrogen bonding, followed by a locking in of the structure by
polymerization, while ordinary polymer gels first require
polymerization to form a structure. The gelling agent is a
polymerizable bis(ureido)-cyclohexane derivative. The authors
suggest these durable gels may have potential applications in
chemical sensors, chemical separations, and pharmaceutical
methods. QY: Mitch Jacoby 
(Chem. & Eng. News 26 Jan 98) (J. Am. Chem. Soc. 119:12675 1997)


9. A FUNCTIONAL NON-PROTEIN MODEL FOR AN ENZYME CATALYST
As protein catalysts, enzymes are constructed of a large number
of subunits (amino acids), but the active site of an enzyme
usually involves only a small region of the molecule's often
complex geometry. Two interesting questions are 1) how much of an
enzyme is actually necessary for its catalytic activity?; and, 2)
is it possible to construct non-protein analogs of the active
site that show similar catalytic activity? ... ... Wang et al (5
authors at Stanford University, US) report functional models of
the enzyme galactose oxidase that catalytically oxidize benzylic
and allylic alcohols to aldehydes with oxygen under mild
conditions, with the similarity between the models and the
natural system pronounced. The authors suggest that modest
structural mimicry by a simple chemical system can prove
sufficient for unusual catalytic mechanisms that have been
previously unprecedented outside a protein matrix. QY: Britt
Hedman  (Science 23 Jan 98)

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

Related Background:

PREPARATION OF A WHOLLY SYNTHETIC CATALYTIC PEPTIDE LIGASE
In biological systems, proteins are the molecules that do most of
the biological work, and the various proteins are the ultimate
expression of the genome of any organism. As polymers, proteins
are similar to the polymers known to polymer chemists, but the
chemical activities of proteins (and their biological functions)
depend mostly on higher-order folding into specific configur-
ations rather than on quasi-crystalline backbone arrays, as is
often the case in non-biological polymer chemistry. It is these
specific configurations that are responsible for the important
specificity and high catalytic power of the proteins that are
enzymes. The configurations, in turn, are an ultimate result of
amino acid sequences which form the backbone of proteins,
sequences which are not simple, as are the backbone sequences of
most non-biological polymers, but are specific, cryptic (coded),
and heterogenous. Because of these complexities, it was thought
until recently that the laboratory synthesis of new functional
proteins would take place only in the distant future. However,
like many other negative prognostications in science, the distant
future surprises us by becoming the near future and then the
present. Already this year there have been a number of reports of
the synthesis of at least partly functional new proteins. Now Kay
Severin et al (Scripps Research Institute, La Jolla CA US) have
synthesized a mere 33-residue peptide based on the coiled-coil
motif that efficiently catalyzes the condensation of two shorter
peptide fragments with high stereoselectivity (selectivity for
molecular conformation in space). The observed rate enhancement
was 10-fold to 4100-fold, with catalytic efficiency in excess of
10^(4). The authors suggest these results confirm the possibil-
ity for future rational design of functional polypeptides. QY: M.
Reza Ghadiri  (Nature 16 Oct 97)

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

STUDIES OF SYNTHETIC PROTEINS WITH LOW AMINO ACID VARIETY
... David Baker et al (University of Washington, US) have found
that reducing the available amino acid alphabet to only 5 amino
acids is sufficient for the construction of a working protein.
The 5 amino acids in this particular case are isoleucine, lysine,
glutamate, alanine, and glycine, and they were used to construct
the SH3 subunit domain that forms beta-sheets. This domain is a
57-amino-acid chain that normally contains 18 different amino
acids, and it is a known part of many large proteins that act as
chemical messengers. During the research, the authors apparently
created millions of candidate proteins involving various amino
acid sequences until they found a combination and arrangement of
amino acids that produced a protein with the same configuration
as SH3. The authors suggest these results indicate that early
life forms could have created functional proteins with only a
limited repertoire of available amino acids. QY: D. Baker, Univ.
Washington (206) 543-2100 (Nature Structural Biol. October 1997)


10. RHO ENZYMES AND THE ACTIN CYTOSKELETON
Eukaryotic cells are cells that have nuclei bounded by a double-
membrane envelope and organelles that compartmentalize the
cytoplasm. Such cells are found in all animals, plants, algae,
fungi, and protozoa. Actin is a protein that polymerizes into
filaments (actin filaments) of about 6 nanometers in diameter
that comprise part of the cytoskeleton of most eukaryotic cells,
and the cytoskeleton is a dynamic intracellular network consist-
ing of actin filaments, intermediate filaments, and microtubules
in eukaryotic cells. In muscle cells, actin filaments are some-
times called "thin filaments", and in non-muscle cells they are
sometimes called "microfilaments". Intermediate filaments are
cytoskeletal filaments about 10 nanometers in diameter and
characterized by relatively great strength, and microtubules are
hollow cytoskeletal tubules about 25 nanometers in diameter,
composed of the protein tubulin and involved in various aspects
of cell shape and cell motility. Guanosine triphosphate is a
high-energy compound that provides energy to drive other chemical
reactions in biological cells, and the G-proteins are a class of
guanosine triphosphate binding proteins that are membrane-bound
and that serve as signal transducers between the cell surface and
the cell interior. The ras-proteins are a group of G-protein
enzymes that among other things catalyze the hydrolysis of
guanosine triphosphate (they are thus guanosine triphosphatases),
and the rho-proteins are a subgroup of ras-proteins. All of these
proteins have been implicated in trans-membrane cell signaling
and in the effects of such signals on the intracellular cyto-
skeleton. ... ... A. Hall (University College London, UK) reviews
the mediation by the actin cytoskeleton of a variety of essential
biological functions in eukaryotic cells: cell shape, cell
polarity, cell movement, and cell division. The author suggests
that understanding the biochemical mechanisms that control the
organization of actin is a major goal of contemporary cell
biology with implications for health and disease, and that
members of the rho family of small guanosine triphosphatases have
emerged as key regulators of the actin cytoskeleton. In addition,
the interaction of these rho enzymes with multiple target
proteins apparently ensures coordinated control of many other
important cellular activities, including gene transcription and
chemotaxis. QY: Alan Hall 
(Science 23 Jan 98)


11. INTERMEDIATE FILAMENTS AND INTRACELLULAR SCAFFOLDING
Fuchs and Cleveland (2 installations, US) review the molecular
biology of cellular intermediate filaments (cf. previous report),
particularly recent evidence that intermediate filaments provide
a flexible intracellular scaffolding whose function is to
structure cytoplasm and resist external stresses. The authors
suggest that mutations that weaken this structural framework
increase the risk of cell rupture and cause a variety of human
disorders. QY: Don W. Cleveland, Univ. of Calif. San Diego, Dept.
Medicine 619-534-3880 (Science 23 Jan 98)


12. MOTOR PROTEINS AND ORGANELLE TRANSPORT
The interior of a living cell is a dynamic system involving a
dynamic supporting matrix, active synthesis and degradation of a
variety of small and large molecules, and the regulated transport
of various molecular species to local and remote sites within the
cell. Research during the past two decades has provided revel-
ations concerning the molecular biology of a variety of orchestr-
ated movements with the cell interior, particularly movements
producing the transport of cell organelles (organized subsyst-
ems). "Motor proteins" are mechanico-chemical enzymes involved in
locomotion or transport, and there are three families of such
proteins: kinesins, dyneins, and myosins. Kinesins and dyneins
are microtubule based motor proteins, while myosin is a micro-
filament based motor protein. In general, as mechanico-chemical
enzymes, motor proteins convert energy from hydrolysis of nucleo-
tides to mechanical force, and since they are involved in many
important cellular events, the molecular details are currently
the focus of intensive research. ... ... N. Hirokawa (University
of Tokyo, JP) reviews the molecular mechanisms of organelle
transport in cells, particularly the role of the motor proteins
kinesin and dynein. The author suggests that in the near future
we will fully understand how the cell sorts and transports
proteins and lipids to their appropriate intracellular
destinations. QY: Nobutaka Hirokawa 
(Science 23 Jan 98)


13. ON THE FUNCTION OF UNCONVENTIONAL MYOSINS
Myosin is the major structural protein of muscle cells, a large
protein with a molecular weight of about 5 x 10^(5) daltons, but
there are several types of myosin found in non-muscle cells,
where they are active in cell movements, and at the present time
more than a dozen different structural classes of myosin are
recognized. The class found in muscle cells (and also in some
non-muscle cells) is well-characterized, but the other classes of
myosin (called "unconventional myosin") are not well-character-
ized, and there is much research underway to relate structure to
function in these important cell constituents. As a group, the
unconventional myosins are apparently involved in many aspects of
cell morphological and functional specialization in all eukary-
otic organisms. ... ... Mermall et al (3 authors at Yale Univ-
ersity, US) review the importance of the myosin superfamily of
actin-based molecular motors in a variety of cellular functions,
including membrane trafficking, cell movements, and signal
transduction. Myosin genes have been identified as targets for
disease-causing mutations. The authors suggest the present task
is to decipher how the myosins function at both the molecular and
cellular levels. QY: Mark. S. Mooseker 
(Science 23 Jan 98)


14. A CRITICISM OF THE PRION HYPOTHESIS
Spongiform encephalopathies are a type of brain disease found in
humans and animals and are characterized by macroscopic vacancies
produced by the disease process (the brain has a sponge-like
appearance). "Transmissible spongiform encephalopathies" such as
bovine spongiform encephalopathy ("mad cow disease") and human
Creutzfeldt-Jakob disease are diseases that apparently involve an
infectious agent. Prions are a class of poorly understood
proteins implicated in transmissible spongiform encephalopathies,
but there is controversy about this, since the details of the
prion infectious process are unknown (cf. background material
below). ... ... Now C. Farquhar (Institute for Animal Health
Edinburgh, UK), in a letter to the journal Nature, notes that the
prion hypothesis is far from proven, and that alternative hypo-
theses of the nature of the causative agent of the transmissible
spongiform encephalopathies are being misrepresented and dismiss-
ed. The "virino" hypothesis, for example, which is not a
conventional virus hypothesis, proposes an agent-specific
replicable informational molecule, yet to be identified, bound to
a protect-ive host prion protein. The author emphasizes that the
precise nature of a prion still eludes identification, and that
the prion hypothesis has yet to explain satisfactorily the many
strains of transmissible spongiform encephalopathies. In
conclusion, the author suggests that the discovery of an
informational molecule with strain-specific properties, for
example a nucleic acid, would refute a prion protein-only
hypothesis, and that until the matter is settled, it should be
recognized there may be more to the biological diversity of
transmissible spongiform encephalopathies than prion protein.
QY: Christine F. Farquhar 
(Nature 22 Jan 98)

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

Related Background:

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)

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

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)

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

PRION DISEASES AND BOVINE SPONGIFORM ENCEPHALOPATHY
... Prions are apparently able to induce certain other proteins
into pathogenic conformations, and these proteins in turn can
cause the same effect in other proteins of the same class. None
of this is yet well understood. One human disease in which prions
have been strongly implicated is Creutzfeldt-Jakob disease (CJD),
which appears to have a genetic basis in about 15% of the cases.
Recently, there has been much concern in Europe concerning the
possible infection of humans who might eat meat from prion-
infected cows. The fears were at first dismissed by the medical
community because of lack of evidence to support the idea, but
recently some evidence has appeared, and the level of concern has
increased significantly. Stanley B. Prusiner, who recently
received the Nobel Prize in Physiology and Medicine for his work
with prions, reviews the relation between prion diseases and the
current bovine spongiform encephalopathy crisis. The author urges
more attention to the fatal disorders of protein conformation
that are apparently involved in prion diseases, and he suggests
studies of prion proteins may have important applications to
understanding Alzheimer's disease, Parkinson's disease, and
amyotrophic lateral sclerosis. QY: S. B. Prusiner, Univ. of
Calif. San Francisco, Neurology (415) 476-4044 (Science 10 Oct
97)

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

... Andrew F. Hill et al (8 authors at 3 installations, UK)
report that the biological and molecular transmission charac-
teristics of a variant of human Creutzfeldt-Jakob disease are
consistent with it being the human counterpart of bovine spongi-
form encephalopathy; and M. E. Bruce et al (13 authors at 4
installations, UK) report that interim results of transmissions
of sporadic classical Creutzfeldt-Jakob disease and the new
variant Creutzfeldt-Jakob disease to mice, such transmissions
producing effects apparently identical to those produced by
transmissions of bovine spongiform encephalopathy to mice,
provide strong evidence that the same agent strain is involved in
both bovine spongiform encephalopathy and Creutzfeldt-Jakob
disease. QY: John Collinge, Prion Disease Group, Imperial Col-
lege, London UK; M. E. Bruce 
(Nature 2 Oct 97)

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

... Rudi Glockshuber et al (Swiss Federal Institute of Tech-
nology) report the first complete determination of the
structure of a full-length prion protein: 208 amino acids,
including a trio of helices and an unfolded tail 97 amino acids
long. Evidence indicates it is the unfolded tail that may be
involved in disease processes. Chemical techniques were used to
reconstitute the folding of the full-length protein, and then
nuclear magnetic resonance was used to determine the structure.
This may be an important step to understanding how prions become
pathogenic. (F.E.B.S. Letters 18 Aug 1997)

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

... Thomas Blattner et al (University of Zurich, CH) report that
mutant mice that do not produce normal PrP cannot be infected by
the scrapie producing prion variant that ordinarily infects mice
that do produce the normal protein. They conclude that transfer
of infectivity to the central nervous system, the major event in
the disease process, is crucially dependent on the expression of
PrP in some as yet unknown tissue compartment. The fact that
there is at least a useful laboratory animal model for the study
of these poorly characterized infectious agents leaves one
optimistic that an understanding of the essentials of prion
pathogenesis may soon be forthcoming. QY: Adriano Aguzzi
 (Nature 4 Sep 1997) 


15. A NEW PROTEIN THAT ACTS AS AN EMBRYOLOGICAL HEAD INDUCER
Hans Spemann, who was awarded the Nobel Prize in Physiology and
Medicine in 1935 for his work in embryology, introduced into
embryology the idea of "organizers", regions of a developing
embryo that determine the future differentiation of adjacent
tissue. In embryological development, the term "induction" refers
to the interaction between two groups of cells in which a
chemical signal (the inducer) from one group causes the other
group to change its developmental path. Members of the gene
family wnt encode secreted glycoproteins (Wnt proteins) that
are required for a variety of developmental processes, ranging
from simple differentiation of cell lineages in primitive forms
to the control of differentiation of the central nervous system
of higher vertebrates. In adult vertebrates, Wnt genes are also
implicated in tissue homeostasis (equilibrium regulation) and
oncogenesis (genesis of cancer cells). ... ... Glinka et al (6
authors at Deutsches Krebsforschungszentrum Heidelberg, DE)
report the identification of the gene dkk-1 (dickkopf-1), which
encodes the protein Dkk-1, the protein apparently a secreted
inducer of Spemann's organizer in the frog (Xenopus) and a member
of a new protein family. The authors suggest their evidence
indicates that dkk-1 is necessary and sufficient to cause head
induction, that dkk genes encode a family of secreted Wnt
inhibitors, and that it is odd that the vertebrate head, which is
thought to be a novel evolutionary structure, should form by
default (i.e., inhibition of Wnt and other activators).
QY: Christof Niehrs, Deutsches Krebsforschungszentrum, Im
Neuenheimer Feld 280, D-69120 Heidelberg, DE (Nature 22 Jan 98)

(continued in Part 3)

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

SCIENCE-WEEK - Part 3/3

A Free Weekly Digest of the News of Science

February 6, 1998

Contents of Part 3:

16. On the Chemistry and Neurophysiological Action of Vanilloids
17. The Role of Visual Experience in Development of Visual Cortex
18. Phantom Sensations Evoked by Human Thalamic Microstimulation
19. An HIV Protein That Protects the Host Cell Against T-Cells
20. Evidence for Axonal Transection in Multiple Sclerosis Lesions

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

16. ON THE CHEMISTRY AND NEUROPHYSIOLOGICAL ACTION OF VANILLOIDS
The compounds called "vanilloids" contain the homovanillyl group
in their structures and they are usually strong irritants with
some interesting analgesic properties. Capsaicin is the pungent
entity in red peppers, and resiniferotoxin (RTX) is an irritant
from the latex of a cactus-like plant (Euphorbia resinifera). An
"analgesic" is any substance (narcotic or non-narcotic) that
relieves pain. An enantiomer is an optical isomer of a compound,
and an "asymmetric synthesis" is a chemical synthesis that
produces a pure or predominantly pure enantiomer rather than a
mixture of isomers. ... ... In a review of the chemistry of
vanilloids and the pharmacology of vanilloid receptors, the
journal Chemical & Engineering News notes 2 important recent
advances in the field. First, Julius et al (University of
California San Francisco, US) (Nature 389:816 1997) have cloned
the gene for the capsaicin receptor, and large quantities of this
receptor are now available for research to test potential
analgesics and guide the development of new drugs; and, second,
the first total asymmetric synthesis of resiniferotoxin by
Jesudason et al (Stanford University, US) (J. Am. Chem. Soc.
119:12976 1997), which makes possible the production of
laboratory analogs. QY: A. Maureen Rouhi 
(Chem. & Eng. News 26 Jan 98)

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

Related Background:

ANALYSIS OF A PAIN PATHWAY ION CHANNEL
Capsaicin is the main pungent ingredient in chili peppers,
producing a sensation of burning pain by selectively activating
sensory neurons that convey information about noxious stimuli to
the central nervous system. Ion channels are protein channels in
cell membranes that allow ions to pass from extracellular
solution to intracellular solution and vice versa. Most ion
channels are selective, allowing only certain ions to pass, and
an individual cell has ion channels with various ion select-
ivities. The selectivity of an ion channel can be "gated", the
channel effectively opened or closed, and ion channels are said
to be voltage-gated or ligand-gated, depending on how the change
in selectivity is provoked. ... ... Michael J. Caterina et al
(University of California San Francisco, US) now report the
isolation from sensory neurons of a functional DNA sequence
encoding the capsaicin receptor, and they observe that the
receptor is a nonselective ion channel that also acts as a heat
receptor. The authors suggest this receptor may be involved in
various human disease states ranging from congenital pain
insensitivity to chronic pain syndromes, and that their cloning
technique may provide a molecular probe for the development of
new analgesic agents. QY: David Julius 
(Nature 12 Oct 97)


17. THE ROLE OF VISUAL EXPERIENCE IN DEVELOPMENT OF VISUAL CORTEX
The visual system of vertebrates, especially that of the higher
vertebrates, is highly organized. The retina of the eye, for
example, which is essentially a surface upon which photons
impinge to be absorbed by chemical photosensors, is "mapped" by
exiting nerve fibers, and light-induced activation of the retinal
map are relayed with some transformations to various levels of
the central nervous system and finally to what is called the
"primary visual projection area" of the cerebral cortex (also
called "primary visual cortex"). The processing of this mapping
information is, in fact, the key to how we perceive the world
around us. ... ... Crair et al (3 authors at 2 installations, US)
report a study of the development of cortical maps for orient-
ation and eye preference in the primary visual cortex of normal
and binocularly deprived cats. These cortical maps were present
by 2 weeks after birth, and developed until nearly 3 weeks of age
whether or not the eyes were open. With continued visual depriv-
ation, responses to both eyes deteriorated. The authors suggest
that the basic structure of visual cortical maps is innate, but
experience is essential for specific features as well as for
maintaining the responsiveness and selectivity of cortical
neurons. QY: Michael P. Stryker 
(Science 23 Jan 98)

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

Related Background:

NEURONAL MECHANISM OF VISUAL CONTRAST ADAPTATION
Adaptation is a fundamental sensory process that allows
organisms with nervous systems to respond to new events in the
environment. Visual contrast adaptation in mammals is achieved
and regulated by nerve cells in the brain visual cortex, but the
detailed mechanism has been unknown. Now Matteo Carandini and
David Ferster (Northwestern University, Evanston IL), using
microelectrodes to monitor the activity of individual nerve
cells in the visual cortex of cats exposed to prolonged visual
stimuli, have demonstrated that the adaptation process involves
chronic changes in the membrane potentials of neurons, such
changes apparently produced by excitatory input. The end result
of the chronic changes is a lowered excitability and effective
adaptation of the neurons themselves. (Science 9 May 97)

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

EVIDENCE OF CROSS-MODAL PLASTICITY IN BLIND HUMANS
In neurobiology, the term "plasticity" is the name given to the
capacity of neural tissue to adjust to change. One variant of
this concerns the dependence of the "wiring" of the nervous
system on its input. Another variant concerns the degree to which
one region can under certain conditions assume the function of
another region. Plasticity does not occur everywhere in the
nervous system, but it is often evident in the cerebral cortex of
the brain, the cortex being the thin layer of cells apparently
responsible for higher analysis of sensory input, language,
ideation, and other so-called higher functions lumped together in
the category "cognitive processes". Last week Leonardo G. Cohen
et al (11 authors at 4 installations in US, AR, JP) reported the
results of studies of cross-modal plasticity in blind humans.
These studies involved non-invasive interference with cortical
activity by applying transient magnetic stimulation from outside
the skull. It has been demonstrated that such stimulation can
affect brain activity, and in this study the apparatus threshold
for stimulation of the motor cortex was first determined, and
then transient magnetic stimulation 10% above that threshold
applied to the occipital lobes of the brain through the overlying
skull to interfere with electrical activity in the visual cortex.
The experiments involved various location and procedural
controls, and also a group of sighted individuals. Essentially,
what was found is that in people blind from an early age, the
visual cortex is apparently involved in somato-sensory function
(fingertip reading of individual Braille characters), while the
same is not true for sighted subjects.
QY: L.G. Cohen  (Nature 11 Sep 97)

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

... One striking example of plasticity concerns the so-called
"critical period" for histological development of the visual
system in mammals. This is a period between birth and a later
time during which the neuron circuits in the visual areas of the
cerebral cortex are being developed. Once the system is comp-
letely developed, keeping one or both eyes closed has no effect
on vision. For example, an adult human can develop a cataract in
one eye, not have it removed for years, but once it is removed
and a lens substitute in place, the vision in that eye is normal.
The critical period for vision in humans lasts from birth to
about 6 years, and there is much histological evidence that the
visual cortex is changing during that time. A similar critical
period exists in other mammals. If both eyes are kept covered
from birth throughout the critical period in cats and monkeys,
and the eyes are then uncovered, the animals remain functionally
blind. It can be shown there is a gradation of the effect of the
absence of input from the eyes: the effect is greater during the
early part of the critical period than later on. And damage can
also be demonstrated by keeping only one eye covered. In all of
this, the eyes themselves are optically normal after they are
uncovered, the cells in the retina and in the lower visual
centers appear to function normally in their response to visual
input. But the deprived eye or deprived eyes are "blind", and the
changes or lack of development responsible for this loss of
visual function are in the visual cortex and are due to its
plasticity, its dependence on appropriate input for the formation
of working connections. (from Science-Report 26 Sep 97)


18. PHANTOM SENSATIONS EVOKED BY HUMAN THALAMIC MICROSTIMULATION
One of the most fascinating phenomena in human neurobiology is
the so-called "phantom limb", the essentials of which are as
follows: Our sensations are based on sensory information arriving
at the higher centers of the central nervous system, the
connections being for the most part "hard-wired" through
embryology and early development. The sensory cerebral cortex, in
fact, quickly develops a hard map of all the peripheral sensory
receiving elements in the body, and the map is thus fixed. Now
consider the amputation of a leg. The relevant peripheral sensory
neurons have cell bodies close to the spinal cord and long axons
that extend to the lower leg. If the lower part of the leg is
removed, the sensory axons are cut at the stump, but the sensory
neuron cell bodies are still intact and most of these cells
survive the amputation. But input from these particular neurons
is hard-wired in the brain to represent input from the lower leg.
So although the lower leg is now absent, anything that excites
the axons of these particular neurons will be interpreted by the
central nervous system as an input from the lower leg as if the
lower leg had not been removed at all. Hence, the term "phantom
limb". In particular, amputees can often feel pain in part or all
of a limb that no longer exists. A stereotaxic device is a rigid
metal coordinate frame into which the head of an animal or human
is fixed so that microscale positioning of electrodes at any
particular coordinate position can be effected without displace-
ment caused by movement of the subject and with some fidelity as
far as the locus of placement at a point is concerned. "Function-
al stereotactic mapping" refers to using a stereotactic device to
map a particular region of the brain under conditions in which
that particular region is functional. The thalamus is an
important part of the sub-cortical brain relaying sensory inform-
ation to the cerebral cortex, and the ventrocaudal thalamus is a
subregion of the thalamus. ... ... Davis et al (6 authors at
University of Toronto, CA), in experiments designed to assist the
treatment of severe phantom or stump pain, report that micro-
electrode recordings and microstimulation during functional
stereotactic mapping of the ventrocaudal thalamus in human
amputees reveals an unusually large thalamic stump representation
consistent with the findings from animal experiments. The authors
suggest their results support the hypothesis that the thalamic
representation of the amputated limb remains functional in
amputees with phantoms.
QY: Karen D. Davis 
(Nature 22 Jan 98)


19. AN HIV PROTEIN THAT PROTECTS THE HOST CELL AGAINST T-CELLS
T-cells are small circulating lymphocytes arising in bone marrow
and maturing into various subtypes in the thymus or as a result
of exposure to a hormone released by the thymus. The T-cells have
a variety of involvements, including the cellular immune
responses, graft rejection, and delay of allergic reactions.
Helper T-cells provoke the production of antibodies by B-cells of
the immune system. Cytotoxic T-cells lyse (kill by rupturing:
lysis) virus-infected cells. The virus called HIV (human immune
deficiency virus) exhibits great specificity for the helper
T-cells of the human immune system, and HIV-1 is the subtype of
HIV that causes most cases of AIDS in the Western Hemisphere,
Europe, and Central, South, and East Africa. The term "epitope"
refers to the region of an antigen molecule responsible for its
specificity in an antigen-antibody interaction: the epitope is
recognized by the antigen-binding site of a specific antibody
molecule. The term "viral epitope", in the context of this
report, refers to a viral-origin epitope that is expressed on the
surface of virus-infected host cells. ... ... Collins et al (5
authors at 5 installations, US) report a study of the ability of
cytotoxic T-cells to recognize and kill HIV-1 infected primary T-
cells, and that cytotoxic T-cells inefficiently lysed infected
primary cells if the viral nef gene protein product (Nef) was
expressed. The authors suggest that the protein Nef protects HIV-
1 infected cells by reducing the viral epitope on their
surfaces.
QY: David Baltimore  (Nature 22 Jan 98)


20. EVIDENCE FOR AXONAL TRANSECTION IN MULTIPLE SCLEROSIS LESIONS
Multiple sclerosis (also known as MS) is a neurological disease
that begins slowly and continues throughout life. The disease is
characterized by loss of the myelin covering of the nerve fibers
of the brain and spinal cord, and there is no cure. It has always
been thought that the myelin loss, which results in the loss of
axon function, is the pathological process producing the
symptoms. This week the neurological community was astounded by
new results that indicate the classic idea is less than complete.
... ... Trapp et al (6 authors at 3 installations, US NO) report
a study of brain tissue obtained at autopsy from 11 patients with
multiple sclerosis and 4 control subjects without brain disease.
In the multiple sclerosis patients, they observed a total of 47
brain lesions, all of which showed evidence of axonal transect-
ion. The authors conclude that transected axons are common in the
lesions of multiple sclerosis, and they suggest that axonal
transection may be the pathological correlate of the irreversible
neurological impairment in this disease. QY: Bruce D. Trapp,
Dept. of Neurosciences, Cleveland Clinic Foundation, 9500 Euclid
Avenue, Cleveland, OH 44195 US. (New England J. Med. 29 Jan 98)

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

Related Background:

HERPESVIRUS LINKED TO MULTIPLE SCLEROSIS
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 a special sheath called myelin. 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 class-
ical physics of electrical transmission lines and the electrical
parameters of nerve fibers, is that the propagation of an electr-
ical pulse along such nerve fibers occurs at a velocity much
higher than that found in unmyelinated fibers. Multiple sclerosis
is a human disease characterized by the progressive loss of the
myelin of the brain and spinal cord, with the physiological
disruptions to be expected from such loss, considering the
significance of myelin in the functioning of nerve cells. The
herpesviruses are a class of viruses producing the complex of
herpes diseases, and HHV-6 is a recently discovered strain of
herpesvirus that apparently causes an infant and early childhood
disease called roseala infantum. Jacobson et al (National Instit-
utes of Health, US) report that a study of multiple sclerosis
patients (36 patients and 66 controls) revealed that 70% of these
patients were infected with the strain of herpesvirus HHV-6. They
also report that magnetic resonance imaging detected numerous
myelin lesions in the brain of a deceased multiple sclerosis
patient, and an autopsy revealed HHV-6 in the lesions but not in
the adjoining normal tissues. Some multiple sclerosis specialists
are expressing reservations about the interpretation of these
results, stating it is possible the viral infection is a
consequence rather than a cause of multiple sclerosis. QY: Steven
Jacobson, National Institute of Neurological Disorders and
Stroke, NIH, Bethesda, MD 20892-0148
(Nature Medicine December 1997)

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

BOOK NOTES

L. Branscomb and J. Keller: INVESTING IN INNOVATION
Creating a Research and Innovation Policy That Works
M.I.T Press, 1998, 516p, US35
An analysis of US science and technology policy. An expansion of
a nonpartisan commissioned report released in Washington April
1997. The authors offer "a new set of technology policy
principles" to provide guidelines for stimulating technical
innovation, shaping public/private partnerships, and establishing
criteria for federal investments in research. The authors are
public policy specialists.

Sankar Chatterjee: THE RISE OF BIRDS
225 Million Years of Evolution
Johns Hopkins Univ., 1998, 312p, 39.95
The author is a paleontologist and the discoverer of Protoavis,
an apparent avian precursor fossil that predates Archaeopteryx by
75 million years. An analysis of bird evolution and anatomy.

L. Dingus and T. Rowe: THE MISTAKEN EXTINCTION
Dinosaur Evolution and the Origin of Birds
W.H. Freeman, 1998, 332p, US34.95
The authors, both paleontologists, are firmly in the camp that
birds are evolved dinosaurs. A comprehensive reference work on
dinosaurs and bird lore.

P. Liss and R. Duce (eds.): THE SEA SURFACE AND GLOBAL CHANGE
Cambridge Univ., 1997, 519p, US95
3 working group reports and 13 individual contributions arising
from a workshop held in 1994. The focus is the physics,
photochemistry, and biology of the sea surface microlayer,
operationally defined as the top 1 millimeter of the ocean
surface. There is not much on the effects of global change on the
microlayer, but this book will be a definitive reference in sea
surface research.

Roy Porter: THE GREATEST BENEFIT TO MANKIND
A Medical History of Humanity from Antiquity to the Present
HarperCollins, 1997, 831p, UK24.99
A valuable reference for anyone interested in the history of
Western medicine. The focus is medicine itself, rather than
various social aspects. Only token chapters on Indian and Chinese
medicine.

M. Rayner-Canham and G. Rayner-Canham (eds.):
A DEVOTION TO THEIR SCIENCE
Pioneer Women of Radioactivity
Chemical Heritage Foundation, 1997, 307p, US55, paper US19.95
(Co-published with McGill-Queens Univ. Press)
A collection of biographical essays concerning 23 women
physicists and chemists in the field of radioactivity in the
first part of the 20th century. The book is noteworthy for
including nearly forgotten women scientists who worked at a time
when established science did its best to discriminate against
them. Physicist and Nobel Laureate (1935) James Chadwick, noting
that radioactivity counting in Vienna was done exclusively by
women, said women "can concentrate more intensely than men,
having little on their minds anyway." 

Pat Shipman: TAKING WING
Archaeopteryx and the Evolution of Bird Flight
Simon & Schuster, 1998, 336p, US25
A popularized but authoritative account of the last 100 years of
avian paleontology. The focus is on the discovery and analysis of
Archaeopteryx as an intermediate form. The author is a
paleontologist.

Ullman: ENCYCLOPEDIA OF INDUSTRIAL CHEMISTRY
Fifth Edition
Wiley-VCH, 1998, print US14,100, CDROM US14,300
37 volumes. Designed as a reference work for science and
engineering libraries. The CDROM is apparently set to expire 18
months after publication, and use beyond that date requires an
"archival license". Annual CDROM updates at US1150. The price of
the print and CDROM versions purchased together is US16,450. This
is another example of library costs definitely not reduced by
electronic publishing.

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