ScienceWeek

SCIENCE-WEEK - Part 1/3

A Free Weekly Digest of the News of Science

This issue is dedicated to the memory of one of our subscribers,
David N. Schramm, astrophysicist, killed in an accident this
past December 19th at the age of 52. He will be missed.

February 20, 1998
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"There are living systems, there is no `living matter'."
-- Jacques Monod

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Contents of This Issue:

Part 1:
1. An Essay on the Great Asymmetry
2. Determination of HDO/H(sub2)O Ratio in Hale-Bopp Comet
3. Determination of Water in the Stars Betelguese and Antares
4. Stellar Origin of Early Solar System Nuclides
5. On the Bose-Einstein Condensate
6. An Exchange of Letters Concerning Fractality in Nature
7. Electric Field-Induced Demixing in Lipid Bilayer Membranes
8. Discovery of 3-Dimensional Algae and Animal Embryo Fossils

Part 2:
9. Precambrian Sponges with Cellular Structures
10. A Model for the Evolution of the Genetic Code
11. Mitochondrial DNA Recombination in a Natural Population
12. Opening of Liposomal Membranes by Talin
13. Evidence that DNA is a Poor Electron Conductor
14. A Transmembrane Form of the Prion Protein
15. On the Resistance of Bacteria to Antibiotics

Part 3:
16. On the History and Applications of Functional Brain Imaging
17. Identification of HIV-1 Sequence in 1959 Human Viral Sample
18. On the Role of Chemokines in Cell Biology and Disease
19. On Protein Folding in Prion and Amyloid Diseases
20. On Grandmothering, Menopause, and Human Evolution  

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1. AN ESSAY ON THE GREAT ASYMMETRY
The zoologist Stephan Jay Gould, in an essay concerning the uses
and misuses of science, and public attitudes toward science, and
in particular the perpetual quandary concerning the positive and
negative potentials of science, dismisses the myths that science
is either intrinsically good or intrinsically evil, and intro-
duces what he calls "the great asymmetry", an intrinsic aspect of
the applications of science that can be viewed as the origin of
public ambivalence toward scientific progress. The idea of the
great asymmetry is that the beneficial applications of science
are usually incremental and incrementally produce adaptive
systems in a complex structure over time (e.g., advanced civiliz-
ations), while the destructive applications of science can in a
relatively short period of "building" time be truly catastrophic
(e.g., the murder of millions by a single dictator). In essence,
the idea is that it is usually easier to destroy a house than to
build a house, and it is this great asymmetry that must be
addressed and explained to the public. Gould concludes: "In any
case, we have no choice, for humans must wonder, ask, and seek --
and science must therefore break through the strictures of custom
to become either our greatest glory, and our most potent engine
of benevolent change, or an accelerator of destruction on the
wrong side of the great asymmetry." QY: Stephen Jay Gould,
Harvard University 617-495-1000 (Science 6 Feb 98)


2. DETERMINATION OF HDO/H(sub2)O RATIO IN HALE-BOPP COMET
One of the important questions concerning the origin and
evolution of the solar system concerns the origin of the various
water reservoirs in the system and the role played by comets
(which apparently consist mostly of frozen water) in delivering
water to various planets and planetary satellites. In the context
of this report, the term "protosolar ratio" refers to the
deuterium/hydrogen ratio in water in the molecular cloud that
condensed to form the Sun and solar nebula that formed the
precursor of the solar system. The James Clerk Maxwell telescope
is a 15 meter diameter radio telescope at an altitude of 4100
meters on Mauna Kea, Hawaii (US), funded by UK CA NL governments.
... ... Meier et al (8 authors at 3 installations, US CA FR)
report the detection of deuterated water (HDO) in comet Hale-Bopp
(C/1995 O1), using the James Clerk Maxwell telescope. The
inferred deuterium/hydrogen ratio in the water is (3.3 +- 0.8) x
10^(-4), a result consistent with measurements of the Halley
comet and with measurements of the Hyakutake comet. The authors
suggest this deuterium/hydrogen ratio, which is higher than that
in terrestrial water, and more than 10 times the estimated proto-
solar ratio, implies that comets cannot be the only source for
the oceans on Earth. QY: Roland Meier, Univ. of Hawaii 808-956-
8975 (Science 6 Feb 98)


3. DETERMINATION OF WATER IN THE STARS BETELGUESE AND ANTARES
The "red giant" stars are stars with surface temperatures between
2000 and 4000 degrees kelvin (relatively "cool" stars) and a
diameter 10 to 1000 times greater than the Sun. They are one of
the final phases in the evolution of a normal star, reached when
the central hydrogen core has been exhausted, and a shell of
hydrogen around the helium core is burned, resulting in a
tremendous inflation of the star's size. Betelgeuse is a red
supergiant star about 500 times the diameter of our Sun and a
strong infrared radiation source in the Orion constellation.
Antares is also a red supergiant, 285 times solar diameter, and
the brightest star in the constellation Scorpius.
... ... Jennings and Sada (2 installations, US MX) report the
identification of absorption lines of hot water in the infrared
spectra of Betelgeuse (alpha-Orionis) and Antares (alpha-Scorpii)
near 12.3 micrometers (wave-numbers 811-819), and that the water
lines originate in the atmospheres of these cool stars and not in
circumstellar material. The authors suggest that from the water
spectra, the upper limit for the temperature of the line
formation region in both stars is 2800 degrees kelvin, with a
water abundance relative to atomic hydrogen of about 10^(-7). QY:
Donald E. Jennings, NASA Goddard Space Flight Center, Greenbelt,
MD 20771 US (Science 6 Feb 98)


4. STELLAR ORIGIN OF EARLY SOLAR SYSTEM NUCLIDES
The nuclides are the various finite lifetime (e.g., > 10exp(-10)
seconds) nuclear species of any particular atom, such as the
finite lifetime isotopes of an atom. ... ... Sahijpal et al (5
authors at 2 installations, IN US) report a correlation between
the initial abundance of (sup41)Ca and (sup26)Al in samples of
apparently primitive meteorites (as inferred from respective
decay products (sup41)K and (sup26)Mg), implying a common origin
for the short lived nuclides. The authors suggest a single
stellar source was responsible for generating these nuclides, and
that the data constrain to less than one million years the
timescale for the collapse of the protosolar cloud to form the
sun and conflict with the idea that the production of short-lived
nuclides resulted from energetic particle interactions within the
protosolar molecular cloud or subsequent solar nebula. QY: J.N.
Goswami  (Nature 5 Feb 98)


5. ON THE BOSE-EINSTEIN CONDENSATE
In 1997, Steven Chu, Claude Cohen-Tannoudji, and William D.
Philips shared the Nobel Prize in Physics for their work in the
1980s involving laser-cooled atoms, work that ultimately led to
the cooling of atoms to extremes close to absolute zero degrees
kelvin, and finally to the creation by Anderson et al (Science
269:198 1995) of a Bose-Einstein condensation in a dilute gas of
rubidium atoms. The essential idea behind these techniques
involves a reduction in the momentum of an atom when it absorbs a
photon. Bose-Einstein statistics is the statistical mechanics of
a system of indistinguishable particles for which there is no
restriction on the number of particles that may simultaneously
exist in the same quantum energy state. Bosons are particles that
obey Bose-Einstein statistics, and they include photons, pi
mesons, all nuclei having an even number of particles, and all
particles with integer spin. In low temperature physics, the
Bose-Einstein condensation is a phenomenon that occurs in the
study of systems of bosons: below a critical temperature, the
quantum ground state becomes highly populated, individual wave
equations merging into a single wave equation, the particles
indistinguishable, and the condensate of particles behaving as a
singe entity. ... ... In a review of the first laboratory study
and recent experiments concerning the Bose-Einstein condensate,
Cornell and Wieman suggest that the Bose-Einstein condensate can
be thought of as the matter counterpart of the laser -- except
that in the condensate it is atoms, rather than photons, "that
dance in perfect unison", and that over the next several years
new experimental observations will improve our understanding of
this singular state of matter, and "the quantum mechanical world
will come a bit closer to our own." QY: Eric A. Cornell, Univ. of
Colorado 303-492-1411 (Scientific American March 1998) 


6. AN EXCHANGE OF LETTERS CONCERNING FRACTALITY IN NATURE
A fractal is a geometrical shape whose structure is such that
magnification by a given factor reproduces the original object.
During the past several decades, the idea that fractal geometry
is an appropriate geometry to describe nature has been proposed
by many researchers. The mathematical constructs involved are
appealing because of their symmetries, and as in the development
of many appealing ideas, the use of the term "fractal" has
increased to the point where experimental observations in all the
sciences are being analyzed and interpreted as examples of
systems with apparently fractal properties. A recent article by
Avnir et al (cf., background item below) that reported a
literature review of experimental determinations of "fractal"
properties of various natural systems has provoked some
controversy and an exchange of letters on the subject, including
a letter from B. Mandelbrot, a chief proponent of the idea of the
universality of fractal geometries in nature. The Avnir group,
reviewing a large number of Physics Review journals papers,
reported that much of the quantitative data that have been
interpreted as identifying systems with fractal geometries do not
in fact satisfy the stringent mathematical requirements for
fractality, and there is thus no evidence that nature can be
described by a fractal geometry. In his response to the Avnir et
al report, Mandelbrot (Yale University, US) suggests the Avnir
group has dwelled on the statistics of implied and possible
failures, rather than on the variety and quality of the best
work, and that in the case of fractal geometry, the best work is
outstanding. Mandelbrot says many of the weak published evidences
of fractality are due to "enthusiasm, imperfectly controlled by
refereeing, for a new tool that was (incorrectly) perceived as
simple." P. Pfeifer (University of Missouri, US) says in a
contiguous letter that "the discovery of fractals requires a lot
more than fitting a power law through a set of points and asking
how many decades of length it spans." In the final letter, Avnir
et al (4 authors at Hebrew University, IL) respond that their
paper reported on "most comprehensive survey of experimental
measurements of fractals done thus far", and that Mandelbrot's
reaction to the outcome of the analysis is "uncalled for", and
that the central question of the "abundance of fractals"
determines either their central relevance to all fields of
natural sciences or their esotericity. Avnir et al say, "the data
we analyzed is not junk and cannot be dismissed: it comes from a
prestigious set of journals in the physics community, and they
represent beyond doubt the status of fractals in the natural
sciences."
QY: Benoit B. Mandelbrot, Yale University, Dept. Mathematics 203-
432-3791; Peter Pfeifer ;
David Avnir  (Science 6 Feb 98)

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

Related Background:

FRACTALS AND THE GEOMETRY OF NATURE
... To the mathematician ... the definition of the property of
"fractality" involves a quantitative requirement of infinitely
many orders of magnitude of power-law scaling of the parameters
of the system -- certainly at least a spanning of many orders of
magnitude. Avnir et al (3 authors at 2 installations, IL), in a
review of the application of the mathematics of fractals to the
geometry of natural systems, point out that the application of
the term "fractal" by scientists to such systems is often
unjustified. The authors surveyed all experimental papers
reporting fractal analysis of data that appeared during a 7 year
period in Physical Review journals (Phys. Rev. A to E, and Phys.
Rev. Lett., 1990-1996), and found that in most cases the order of
magnitude spanning required for mathematical fractality was not
achieved, and that the use of the term "fractal" in these
contexts has at most a heuristic value. The authors suggest there
is at present no experimental evidence that the geometry of
nature is fractal. QY: David Avnir 
(Science 2 Jan 98)


7. ELECTRIC FIELD-INDUCED DEMIXING IN LIPID BILAYER MEMBRANES
In this report, the term "critical demixing" refers to the
formation of lateral concentration gradients in a two-dimensional
system at or near the critical point for the system -- the
thermodynamic state variable point at which the system is not
phase distinguishable. A "bilayer" membrane is a membrane
consisting of two contiguous monomolecular layers, and such
layers, involving lipid molecules with polar groups, are
important in biological systems. ... ... Groves et al (3 authors
at Stanford University, US) report a method to study critical
demixing in bilayer membranes by using an electric field applied
tangent to the plane of a confined patch of a supported lipid
bilayer, and provide a thermodynamic model of the system to
analyze the results. The steady-state distribution of lipids
under the influence of an electric field is very sensitive to
demixing effects, even at temperatures well above the critical
temperature for spontaneous phase separation. The authors suggest
this may have significant consequences for organization and
structural changes in natural cell membranes.
QY: Harden M. McConnell 
(Proc. Natl. Acad. Sci. US 3 Feb 98)


8. DISCOVERY OF 3-DIMENSIONAL ALGAE AND ANIMAL EMBRYO FOSSILS
A phosphorite is a sedimentary rock composed chiefly of phosphate
minerals. The Proterozoic era (also called the Algonkian) is the
geologic time between the Archean and the Paleozoic, with the
Archean beginning about 3.9 billion years ago and involving the
first appearance of sedimentary rocks and the first primitive
organisms at the bottom of the oceans. In paleontology, the term
"radiation" refers to a diverging and diversifying spread of
animals or plants into new environments with a resultant
production of new evolutionary forms, and the Ediacaran radiation
refers to an assemblage (until now the oldest) of soft-bodied
marine animals, the assemblage first discovered in the Ediacara
Hills in Australia. The algae comprise a large mixed group of
photosynthetic and essentially single-celled plants, and are
considered ancestral to modern green plants. Thalli are primitive
types of plant bodies not differentiated into stems, leaves, and
roots; the term also refers to the gametophyte generation (the
phase of the plant life cycle producing reproductive cells) of
some ferns and lichens. The term "cleavage stages" refers to the
early stages of embryo formation when the egg cell rapidly
divides into smaller and smaller cells. The "Bilateria" are a
major division of the animal kingdom comprising all forms with
bilateral symmetry, and the term "bilaterians" refers to the
first such forms appearing after the emergence of protozoa. The
term "phylogeny" refers to the evolutionary history of an
organism or group of organisms. ... ... Xiao et al (3 authors at
2 installations, US CN) report the discovery of phosphorites of
the late Neoproterozoic (570 +- 20 million years ago) in the
Doushantuo Formation, southern China, an apparent exceptional
record of multicellular life from just before the Ediacaran
radiation of macroscopic animals. Abundant thalli with cellular
structures preserved in 3-dimensional detail show that late-
Proterozoic algae already possessed many of the anatomical and
reproductive features seen in modern marine flora. Embryos
preserved in early cleavage stages indicate the divergence of
lineages leading to bilaterians may have occurred well before
their macroscopic traces or body fossils appear in the geological
record. The authors suggest that discovery of these fossils shows
that the early evolution of multicellular organisms is amenable
to direct paleontological inquiry, and that paleontological
observations, together with insights from molecular phylogeny and
developmental genetics, can facilitate a modern integration of
phylogeny, development, and paleontology that extends deeply into
evolutionary history to address the early evolution of
multicellular life. QY: Andrew H. Knoll, Botanical Museum,
Harvard University, 617-495-1000 (Nature 5 Feb 98)

(continued in Part 2)

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

SCIENCE-WEEK - Part 2/3

A Free Weekly Digest of the News of Science

February 20, 1998

Contents of Part 2:

9. Precambrian Sponges with Cellular Structures
10. A Model for the Evolution of the Genetic Code
11. Mitochondrial DNA Recombination in a Natural Population
12. Opening of Liposomal Membranes by Talin
13. Evidence that DNA is a Poor Electron Conductor
14. A Transmembrane Form of the Prion Protein
15. On the Resistance of Bacteria to Antibiotics

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9. PRECAMBRIAN SPONGES WITH CELLULAR STRUCTURES
The sponges (Porifera) are a phylum of primitive multi-cellular
animals (Metazoa), always attached at one point to a substrate,
usually without a definite symmetry, and usually marine. The
sponge body is a loose aggregation of cells with little
intercellular coordination, but the cells are specialized into
various types with various functions important to the viability
of the entire organism. There is also in sponges an internal
"skeleton" of chalk, silica, or protein, and "calcareous sponges"
are sponges containing a relatively large amount of calcium
carbonate. In this report, "spicules" are the hard internal
structures in sponges composed primarily of silica or calcium
salts, and a "monoaxonal" spicule is a spicule having essentially
only one dimension (e.g., needle-like). The term "epidermis"
refers to the outermost layer of cells in any multicellular
organism; "porocytes" are tubular cells that constitute the walls
of certain sponges; "amoebocytes" are freely moving cells (sponge
cells in this context) within a metazoan tissue; "sclerocytes"
are cells involved in the formation of the sponge skeleton;
"spongocoel" refers to the branching internal cavity of a sponge,
the cavity having a connection in one place or another to the
external aqueous environment; "flagella" are long and thin
cellular organelles that protrude from the surfaces of cells and
are specialized to produce locomotion. The Cambrian period
extended from 545 to 505 million years ago, and was the time
during which many multicellular organisms first arose, and the
Vendian period is the Precambrian metazoan fossil period. The
term "Cambrian explosion" refers to the apparent relatively
sudden appearance of an enormous number of living forms during
the Cambrian period. ... ... Li et al (3 authors at 2 install-
ations, TW CN) report the identification of sponge remains in the
Early Vendian Doushantuo phosphate deposit (cf. report #8, this
issue) in south China. The skeletons consist of siliceous
monoaxonal spicules, with preserved soft tissues including the
epidermis, porocytes, amoebocytes, sclerocytes, and spongocoel,
and among thousands of metazoan embryos a sponge larva having a
shoe-shaped morphology and dense peripheral flagella. The authors
suggest the data indicate the calcareous sponges may have an
extended history in the Late Precambrian, and that animals lived
40 to 50 million years before the Cambrian explosion. They
further suggest these Doushantuo rocks provide a potentially
inexhaustible resource for understanding the early evolution of
animal life. QY: Chia-Wei Li, National Tsing Hua Univ., Hsinchu,
Taiwan, China (Science 6 Feb 98)


10. A MODEL FOR THE EVOLUTION OF THE GENETIC CODE
Eukaryotic cells are cells with discrete organelles such as
nuclei, mitochondria, etc. As organelles, the mitochondria, which
are of prime importance in the oxygen metabolism of eukaryotes,
are a special class, since it is generally believed they probably
originated as primitive cells that established themselves in
symbiotic arrangements in the interiors of larger cells. The
mitochondria, in fact, carry their own DNA and thus their own
genetics. In mathematics, a Lie algebra (named after M.S. Lie
1842-1899) is a system of vector fields on a topological space in
which independent quantities are reduced to groupings whose
relationships are then subject to algebraic operations. In the
context of this report, the term "representation theory" refers
to the study of algebraic groups by the use of their represent-
ations, with the representation of a group given by a virtual
"mapping" of the group onto a group of another type. Pyrimidine
and purine are precursors of DNA nucleotide bases. A codon is the
elemental genetic coding unit, a triplet of 3 consecutive
nucleotides that define a specific amino acid. Some amino acids
are determined by more than one codon, leading to a degeneracy
(redundancy) in the genetic code. ... ... Bashford et al (3
authors at University of Tasmania, AU) present a model for the
structure and evolution of the eukaryotic and vertebrate
mitochondrial genetic codes based on the representation theory of
a Lie superalgebra, with a key role played by pyrimidine and
purine exchange symmetries in codon quartets. The authors suggest
that the group theoretical technique is able to give a succinct
account of many of the currently understood aspects of the
evolution of the genetic code and the observed degeneracy
structure of the codon:amino-acid correspondences, and that their
particular model is susceptible to quantitative verification.
QY: P.D. Jarvis 
(Proc. Natl. Acad. Sci. US 3 Feb 98)


11. MITOCHONDRIAL DNA RECOMBINATION IN A NATURAL POPULATION
The term "genotype" refers to the fundamental genetic makeup of
an organism, and in this report the "organism" is the mitochond-
rion. "Clonal" evolution of a DNA code is an evolution involving
point mutations as a result of physical or chemical factors or
specific duplication errors, while "recombination" evolution of a
DNA code is an evolution involving the incorporation of fragments
of DNA from organisms of the same or other species.... ...
Saville et al (3 authors at University of Toronto Mississauga,
CA), using nucleotide sequence data, report that the genotypic
structure of mitochondrial DNA in a natural population of the
fungus Armillaria gallica is inconsistent with purely clonal
mitochondrial DNA evolution and is fully consistent with
mitochondrial DNA recombination. The authors suggest their
results have implications for explanations of discrepancies in
human mitochondrial phylogeny, and for genetic theories of
fitness and long-term survival.
QY: James B. Anderson 
(Proc. Natl. Acad. Sci. US 3 Feb 98)


12. OPENING OF LIPOSOMAL MEMBRANES BY TALIN
Dark-field microscopy is a method that achieves an improvement of
the resolution of the light microscope by using an optical
arrangement for illumination that produces light scattered or
refracted by the object, the object appearing bright against a
dark background. Liposomes are closed vesicles of lipid bilayers
or monolayers, and they have been studied intensively for decades
as model membrane systems and as delivery vehicles for drugs to
cells (effected when the liposome fuses with the cell membrane).
... ... Saitoh et al (4 authors at Nagoya University, JP) report
a study, using direct real-time high intensity dark-field
microscopy, of morphological changes of liposomes caused by
interactions between liposomal membranes and talin, a cyto-
skeleton submembrane protein, and that when talin was added to a
liposome solution, liposomes opened stable holes and were
transformed into cup-shaped liposomes and eventually lipid
bilayer sheets. The morphological changes were reversed by talin
dilution, the sheets transforming back into spherical liposomes.
The authors suggest this is the first demonstration that a lipid
bilayer can maintain a stable free edge in aqueous solution, and
a refutation of the established dogma that all lipid bilayer
membranes inevitably form closed vesicles. They further suggest
that talin may be a useful tool for manipulating liposomes.
QY: Kingo Takiguchi 
(Proc. Natl. Acad. Sci. US 3 Feb 98)


13. EVIDENCE THAT DNA IS A POOR ELECTRON CONDUCTOR
In general, electron transfer is the passage of an electron from
one constituent of a system to another. In recent years, there
have been two views of electron transfer through the DNA double
helix, with one view holding the electron conduction properties
of DNA are that of an insulator and no greater than that of a
protein, and the other view holding that the DNA double helix can
transfer electrons along its length freely enough to make the
double helix an electrical conductor. There are many substances
which, upon absorbing radiant energy at one frequency, then emit
radiant energy at another frequency, the emitted energy at a
lower frequency (which means lower energy) than the absorbed
radiant energy. These substances are said to be "fluorescent",
and they are studied by "fluorescence spectroscopy". Some
substances, for example, will absorb ultraviolet light and then
emit visible light. The fluorescence of these molecules is due to
the electronic properties of certain chemical groups, and some of
these chemical groups can be easily introduced into other
molecules. ... ... Tanaka and Fukui now report determination of
the rate of electron transfer through a DNA system modified to
include the insertion of a fluorescing electron acceptor (9-
amino-5-chloro-2-methoxymeridine). The electron donor guanine was
placed at varying distances from the dye moiety, the system
irradiated, and the resulting fluorescence spectra measured to
calculate the rates of electron transfer from the fluorescence
quantum yields. The electron transfer rate was found to be
comparable to that of proteins, and the authors suggest that DNA-
base stacking does not form a special mediator for the fast
electron transfer process QY: Kazuyoshi Tanaka, Kyoto Univ., JP.
(Angew. Chem. Int. Ed. 37:158 1998) (Chem. & Eng. News 9 Feb 98)


14. A TRANSMEMBRANE FORM OF THE PRION PROTEIN
A transgenic mouse is a mouse into which genetic material from
another organism has been transferred, the transferred and
incorporated new mouse genes then being expressed with the
resultant production of specific proteins. 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"). The "endoplasmic reticulum" is an extensive
system of flattened membranous sacs in the cytoplasm of cells,
important in protein and lipid biosynthesis, translocation of
synthesized molecules, and continuous with the nuclear envelope.
... ... Hegde et al (9 authors at Univ. of California San
Francisco, US) report a study with transgenic mice expressing
prion protein mutations that alter the relative ratios of the
topological forms of the molecule. Expression of a particular
endoplasmic reticulum transmembrane form (Ctm) of the protein
produced neurodegenerative changes in mice similar to those of
some genetic prion diseases, and brains from these mice contained
this form of the protein but not the isoform responsible for
transmission of prion diseases. The authors suggest that aberrant
regulation of protein biogenesis and topology at the endoplasmic
reticulum can result in neurodegeneration, and that proteins
undergoing topological regulation such as Ctm-prion protein may
be involved in neurogenerative diseases besides those currently
attributed to prions. QY: Vishwanath R. Lingappa
; Stanley B. Prusiner, Univ. of Calif. San
Francisco 415-476-4044. (Science 6 Feb 98)


15. ON THE RESISTANCE OF BACTERIA TO ANTIBIOTICS
S. Levy (Tufts University, US), in a review of recent
developments in antibiotic resistance, notes that strains of at
least 3 pathogenic bacterial species -- Enterococcus faecalis,
Mycobacterium tuberculosis, Pseudomonas aeruginosa -- have
already developed resistance to every one of the 100 antibiotic
drugs in use by clinicians. Levy says a change in attitudes of
the public and clinicians concerning the overuse of antibiotics
is badly needed, and that a reversal of increasing bacterial
resistance to antibiotics, as well as increasing resistance of
parasites, fungi, and viruses to antimicrobials and antivirals,
will require a new global awareness of the broad consequences of
anti-pathogen drug usage. QY: Stuart B. Levy, Tufts Univ. School
of Medicine 617-636-6571 (Scientific American March 1998)

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

Related Background:

STUDIES SHOW MARKED INCREASE IN DRUG RESISTANCE OF MICROBES
Widespread use of antibiotics continues to force the evolution of
strains of pathogens resistant to the drugs. For example, the
incidence in the U.S. of microbes resistant to penicillin has
increased fourfold since 1994. At the May 19th International
Conference of the American Lung Association and American Thoracic
Society in San Francisco, researchers from the State University
of New York (Buffalo NY US) and the University of Iowa College of
Medicine (Iowa City IA US) found the increase in resistance of
Streptococcus pneumoniae, a common cause of respiratory
infections, to be dramatic. 10.5% of the samples were highly
resistant to antibiotics and 24.9% moderately resistant. In 1994,
those figures stood at only 3.2% and 14.1%, respectively. In the
Southeastern part of the U.S., 41% of the samples were found to
be resistant. The researchers suggest that the medical community
must be on the watch for rapidly developing epidemics caused by
antibiotic resistant strains of pathogens, and that antibiotics
themselves should be administered only when necessary if we are
to slow down the evolution of these resistant microbes.
(UPI 19 May 97) 

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

APPEARANCE OF A STAPHYLOCOCCUS STRAIN RESISTANT TO VANCOMYCIN
Staphylococcus aureus is a common pathogenic bacterium in
hospitals, and causes thousands of often fatal infections each
year. Vancomycin is an antibiotic of last resort, which is used
when all other antibiotics fail. Now the first case has appeared
in Japan of a 4 year old boy infected with a strain of
Staphylococcus aureus resistant to vancomycin. Health experts
say it is only a matter of time before the pathogen reaches U.S.
hospitals. Fred Tenover, laboratory chief of the U.S. Center for
Disease Control Hospital Infections Branch says, "The strain is
marching up the ladder of resistance... It is not a cause for
panic, but it is a cause for concern." (UPI 28 May 97)

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

REDUCED ANTIBIOTIC USAGE LOWERS BACTERIAL RESISTANCE
To understand the mechanism of the worldwide increase in
bacterial resistance to antibiotics one need only consider that
for all biological organisms most chemical aspects are more or
less displayed as a Gaussian distribution, the so-called "normal"
or "bell-shaped" curve. What this means in the context of
applying an antibiotic to a population of a particular bacterial
species is that something like 10% or 15% of the population will
show much lower than average resistance to the drug, about 60%
will have close to the average resistance to the drug, and about
10% to 15% will show above average resistance to the drug, all
because of the way the chemistry responsible for resistance to
the drug is distributed in the population. These numbers are
variable from one species of bacteria to another, and they also
vary with the antibiotic used, but the general idea is the same.
The result of all of this is that if we use an antibiotic against
a specific bacterial population, those members of the population
that have superior resistance to the antibiotic will survive to
reproduce their genome, most of the others will be killed, and
before long we will have on our hands populations of that species
which are more or less totally resistant to the antibiotic. This
is nothing more than a concrete instance of the idea of
"selection pressure" in evolution. In 1946 about 90% of
Staphylococcus aureus (a common and dangerous pathogen bacterium)
in hospitals were killed by the antibiotic penicillin, which
first became widely available at about that time. By only 6 years
later, 75% of S. aureus caught and cultured in hospitals were
resistant to penicillin, and by the 1970s, 90% of S. aureus,
whether in hospitals or in the community, were resistant to the
drug. There are similar stories concerning other bacterial
species and other drugs, the worst scenarios evidently occurring
in hospitals; but one cannot fault hospitals, because in both
hospitals and the community antibiotics have been routinely
needlessly administered and/or over-administered, with a
consequent selection pressure that produces antibiotic-resistant
pathogens. Can the process be reversed? There may still be some
hope against bacterial species which are not already over-
whelmingly resistant. This week Helena Seppala et al (about 100
authors in FI) report that in Finland, after an organized
nationwide reduction in the use of macrolide antibiotics
(macrolides are large-ring molecules with many functional side
groups) for outpatient therapy, the resistance of group A
streptococci to the common antibiotic erythromycin dropped by
half from 16.5 per cent in 1992 to 8.5 per cent in 1996. In an
editorial in the New England Journal of Medicine, Morton N.
Swartz (Massachusetts General Hospital, Boston US) calls this "an
impressive example of how an enlightened national policy on
antibiotic use can become an effective public health measure."
QY: H. S. Seppala, Antimicrobial Research Laboratory, PO Box 57,
20521 Turku, FI (New England J. Med. 14 Aug 97)

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

NEW MULTI-DRUG RESISTANCE OF PLAGUE PATHOGEN
Plague, also called bubonic plague or "Black Death", is a disease
with a notorious history. It is caused by the bacillus Yersinia
pestis, which infects wild rodents. The bubonic variant of the
disease is transmitted to humans from rodents by the bite of an
infected flea. Human to human transmission occurs by inhalation
of respiratory droplets spread by the cough of patients with
plague who have developed pulmonary lesions, and the result of
this is "primary pneumonic plague", which differs from "bubonic
plague" in that bubonic plague affects the lymph nodes, among
other tissues (producing "buboes", lymph node swellings). The
last plague pandemic began in Hong Kong in 1894 and spread
throughout the world. Plague still exists as an endemic disease
in many parts of the world, including the southwestern U.S.
Prevention of plague is based on rodent control, and the use of
insect repellents to minimize flea bites. Early treatment after
infection with the antibiotics streptomycin, chloramphenicol, or
tetracycline reduces mortality to less than 5%. Nevertheless,
plague is now considered a reemerging disease, with recent
epidemics in a number of countries after an absence of as much as
3 decades. The incidence of the disease has also been spreading
in the U.S. Now Marc Galimand et al (World Health Organization
and the Pasteur Institute, FR) report high-level resistance of Y.
pestis in a clinical isolate in Madagascar to multiple
antibiotics, including resistance to all the drugs recommended
for plague prophylaxis and therapy. The resistant genes are
apparently carried by a plasmid that can conjugate to other Y.
pestis isolates. So this pathogen species, heretofore considered
universally susceptible to antibiotics, is now exhibiting high
and spreadable resistance to these drugs. Epidemiologists are
alarmed and are urging an international effort to deal with the
problem. QY: Elisabeth Carniel, Institut Pasteur, 28 rue du Dr.
Roux, 75724 Paris CEDEX 15, FR. (New England J. Med. 4 Sep 97)

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

APPARENT IRREVERSIBILITY OF BACTERIAL ANTIBIOTIC RESISTANCE
At a recent meeting of the European Society for Evolutionary
Biology (Arnhem NL), several research groups have apparently
independently confirmed the unhappy news that bacteria that have
mutated to exhibit resistance to specific antibiotics do not
evolve susceptible strains when they are no longer exposed to
these antibiotics. Bruce Levin and Bassam Tomah (Emory Univers-
ity, US) report that 25% of bacteria sampled from infant diapers
are strains of E. coli still resistant to the antibiotic strepto-
mycin, which has been rarely used during the past 30 years.
Richard Lenski (Michigan State University, US) has independently
shown that after 20,000 generations in the absence of strepto-
mycin, E. coli still carries the gene that confers resistance to
the antibiotic. The consensus is apparently that a compensatory
mutation has occurred, a mutation that compensates for the loss
of fitness produced by the gene that confers antibiotic
resistance, and which results in long-term survival of the
resistant strain. Levin suggests the same kind of compensatory
mutations "will almost certainly be found in other resistant
bacteria." The implication is that the evolutionary development
of bacterial resistance to antibiotics will not be reversed by
reducing the use of these antibiotics, which means the effective-
ness of these antibiotics is essentially irreversibly lost. QY:
B. Levin, Emory Univ., Population Genetics (404) 727-5660
(Science 24 Oct 97)

(continued in Part 3)

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

SCIENCE-WEEK - Part 3/3

A Free Weekly Digest of the News of Science

February 20, 1998

Contents of Part 3:

16. On the History and Applications of Functional Brain Imaging
17. Identification of HIV-1 Sequence in 1959 Human Viral Sample
18. On the Role of Chemokines in Cell Biology and Disease
19. On Protein Folding in Prion and Amyloid Diseases
20. On Grandmothering, Menopause, and Human Evolution  

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

16. ON THE HISTORY AND APPLICATIONS OF FUNCTIONAL BRAIN IMAGING
The term "functional brain imaging" refers to a number of
different techniques for mapping activity in the brain in
response to external stimuli or during sensory, perceptual, or
cognitive events. Positron emission tomography is a technique for
producing cross-sectional images of the body after ingestion and
systemic distribution of safely metabolized positron-emitting
agents. The images are essentially functional or metabolic, since
the ingested agents are metabolized in various tissues. Fluoro-
deoxyglucose and H(sub2)O(sup15) are common agents used for
cerebral applications, and in cerebral applications of central
importance to the technique is the fact that changes in the
cellular activity of the brains of normal, awake humans and
unanesthetized laboratory animals are invariably accompanied by
changes in local blood flow and also changes in oxygen consump-
tion. Magnetic resonance imaging is a technique involving images
produced by mobile protons of a tissue excited by the application
of a magnetic field, and when used in functional cerebral
imaging, the basis of the technique is that it images very small
metabolic, blood-flow, and perfusion-diffusion changes in vivo,
in real time, and with no risk to the subject.
... ... M. Raichle (Washington Univ. School f Medicine, US)
reviews the new techniques of functional brain imaging: positron
emission tomography and magnetic resonance imaging. The author
suggests these tools provide the potential to provide unparallel-
ed insight into some of the most important scientific, medical,
and social questions facing mankind, and that understanding these
tools should be a high priority.
QY: Marcus E. Raichle 
(Proc. Natl. Acad. Sci. US 3 Feb 98)


17. IDENTIFICATION OF HIV-1 SEQUENCE IN 1959 HUMAN VIRAL SAMPLE
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. ... ... Zhu et al (6 authors at
4 installations, US UK) report the laboratory amplification and
characterization of viral sequences from a 1959 African plasma
sample previously found to be HIV-1 seropositive. Multiple
phylogenetic analyses authenticate this case as the oldest known
HIV-1 infection, and place its viral sequence near the ancestral
node of subtypes B and D in the major group. The authors suggest
their results indicate these HIV-1 subtypes, and perhaps all
major-group associated viruses, may have evolved from a single
introduction into the African population not long before 1959,
and that the diversification of HIV-1 in the past 40 to 50 years
portends even greater viral heterogeneity in the coming decades,
and underscores the need for continued surveillance.
QY: David D. Ho  (Nature 5 Feb 98)

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

Related Background:

ESTIMATED 20 MILLION INFECTED WITH AIDS IN SUB-SAHARAN AFRICA
There is perhaps too much of a tendency in many quarters to think
of a plague only as a state of affairs in which people drop dead
in expensive restaurants and get hauled away in trucks containing
piles of bodies. Our current plague, although not as dramatic as
some plagues of the past, is no less an international calamity.
The United Nations AIDS Program recently released a report
containing the following: -- In 1997, 5.8 million people
worldwide were newly infected with HIV.
-- The number of new HIV infections this year rose 9% over 1996.
-- The total number of infected adults is now a little under 30
million, about 1% of the world's adult population.
-- This year, the total number of people infected with HIV
increased by 13%
-- More than 20 million people in sub-Saharan Africa are infected
with HIV, which is 7% of that adult population.
-- This year, 2.3 million people worldwide will have died of
AIDS, the consequent stage of HIV infection.
-- In South and Southeast Asia, 6 million people are infected
with HIV.
-- In Latin America, 1.3 million people are infected with HIV.
-- In North America, 860,000 people are infected with HIV.
-- In Western Europe, 150,000 people are infected with HIV.
(Nature 27 Nov 97)


18. ON THE ROLE OF CHEMOKINES IN CELL BIOLOGY AND DISEASE
There is intense interest among virologists in chemokines, which
are immune system signaling molecules. The receptors for
chemokines are proteins on the surfaces of cells, and there is
evidence that HIV uses these receptors to force entry into cells.
Leukocytes (also called "white blood cells"), of which there are
5 types, are the primary cells involved in the response of the
vertebrate body to invasion by foreign substances. ... ... A.
Luster (Harvard University, US), in a review of chemokines,
describes how chemokines appear to have the capacity to precisely
control the movements of leukocytes. The author suggests that
although the roles of chemokines in the pathophysiology of
disease are still being defined, there is growing evidence from
studies in animals that the neutralization of chemokine activity
may have therapeutic value. QY: Andrew D. Luster, Harvard Univ.
Medical School 617-432-1550 (New England J. Med. 12 Feb 98)

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

Related Background:

... Now there is new evidence that cytomegalovirus (CMV), a
rather ubiquitous viral entity, may, upon successful invasion of
cells, force the production of a cell surface chemokine receptor
protein called US28, and that US28, in turn, may act as a docking
and membrane fusion locus for HIV. The results were reported by
Olivier Pleskoff et al (Institut Cochin de Genetique Moleculaire,
FR; University of Paris, FR). Up to 80% of the general
population, and almost all HIV-infected homosexual males, are
known to be infected with CMV. If these results are correct, then
virologists will need to shift their thinking to include the
possibility of direct cooperative interaction between different
viral pathogens. (Science 20 Jun 97) 


19. ON PROTEIN FOLDING IN PRION AND AMYLOID DISEASES
What is remarkable about prions (cf. report #14, this issue) is
that although they behave as infectious agents, they are 100
times smaller than viruses and their mechanism of replication is
unknown. 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. Denaturation is an irreversible change in
solubility and other properties of proteins when they are exposed
to various conditions, including heat and an acidic environment.
The denatured protein essentially loses all its higher order
structure and becomes a simple uncoiled/unfolded polymer. A
lysosome is a cytoplasmic membrane-bound vesicle 5 to 8 nano-
meters in diameter and containing a variety of glycoprotein
hydrolytic enzymes used to digest foreign material or defective
organelles. The term "amyloid" refers to a group of chemically
diverse proteins composed of linear nonbranching aggregated
fibrils that occur as pathological extracellular deposits in
various diseases (including several neurodegenerative diseases).
... ... J. Kelly (Scripps Research Institute, US), in a comment-
ary on prion proteins, suggests that the conversion of normal to
pathogenic prion protein likely occurs in the partially denatur-
ing environment of a cellular compartment such as a lysosome,
where the lower pH environment (or another factor-environment)
"effects the conformational changes that facilitate amyloid and
prion self-assembly". The author suggests that using the
structure of normal prion protein to design high-affinity ligands
to what appear to be critical higher-order molecular structure
regions may lead to an understanding of the structural changes
required for pathogenic amyloid fibril formation.
QY: Jeffrey W. Kelly, Scripps Research Institute 619-784-1000
(Proc. Natl. Acad. Sci. US 3 Feb 98)


20. ON GRANDMOTHERING, MENOPAUSE, AND HUMAN EVOLUTION  
Hawkes et al (5 authors at 2 installations, US) present a
hypothesis that the long postmenopausal lifespans that disting-
uish humans from all other primates may have evolved with mother-
child food sharing, a practice that allowed aging females to
enhance the fertility of their daughters, the practice thereby
increasing selection against senescence. The authors suggest
their hypothesis also accounts for human late maturity, small
size at weaning, and high fertility, and that the hypothesis has
implications for past human habitat choice and social organiz-
ation, and for ideas about the importance of extended learning
and paternal provisioning in human evolution.
QY: E.L. Charnov, Univ. of Utah, Dept. of Biology 801-581-5636
(Proc. Natl. Acad. Sci. US 3 Feb 98)

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

BOOK NOTES:

C. Adami: INTRODUCTION TO ARTIFICIAL LIFE
Springer, 1998, 424p, US59.95
An exploration of the theoretical basis for understanding the
dynamics of systems of self-replicating information. CDROM (for
all platforms except Macintosh) with Avida software for
simulation of artificial evolution. From a course at the
California Institute of Technology.

Keith E. Cooksey (ed.):
MOLECULAR APPROACHES TO THE STUDY OF THE OCEAN
Chapman and Hall, 1998, 549p, US199.95 UK110
An introduction to a critical area of environmental biology.
Covers the molecular analysis and ecology of the oceans and
advanced techniques.

R. Huang and K. Yu: STELLAR ASTROPHYSICS
Springer, 1998, 600p, US79
A graduate level text and professional reference. Theoretical
foundations of stellar astrophysics, structure and evolution of
single and binary stars of various masses, theory of stellar
oscillations, numerical models for stellar structure and
evolution, stellar pulsation, model atmospheres and line
formation.

Gina Kolata: CLONE
The Road to Dolly and Path Ahead
Morrow/Allen Lane, 1997, 218p, US23 UK15.99
A detailed account of the history, technology, philosophy, public
concern, and science of cloning in general and specifically the
cloning work of Ian Wilmut at the Roslin Institute. The author is
the science editor of the New York Times.

R. Ormond, J. Gage, M. Angel (eds.): MARINE BIODIVERSITY
Patterns and Processes
Cambridge Univ., 1998, 472p, US74.95
A compilation of key studies from the deep sea, open ocean,
tropical shores, and polar regions. The focus is diversity in
different ecosystems.

R.C. Powell: PHYSICS OF SOLID-STATE LASER MATERIALS
Springer, 1998, 440p, US59.95
A graduate level text and professional reference. Fundamental
physics of solid-state lasers, optical and electronic properties
of laser materials, quantum mechanics, solid-state physics,
spectroscopy, crystal field theory, quantum theory of radiation,
emission and absorption of radiation, nonlinear optics, lattice
vibrations, ion-ion interactions, specific solid-state laser
materials, novel and non-standard laser materials.

H. Sato and M. Fehler: SEISMIC WAVE PROPAGATION AND SCATTERING IN
THE HETEROGENEOUS EARTH
Springer, 1998, 308p, US59.95
A research monograph. Focuses on recent developments in study of
seismic wave propagation and scattering, with emphasis on the
lithosphere.

C.P. Williams: EXPLORATIONS IN QUANTUM COMPUTING
Springer, 1998, 307p, US59.95
A simplified explanation of the field. Includes a CDROM with
simulations and tutorials (Mathematica 2.2 and 3.0 notebooks)

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