ScienceWeek

SCIENCE-WEEK

A Weekly Email Digest of the News of Science

A journal devoted to the improvement of communication
between the scientific disciplines, and between scientists,
science educators, and science policy makers.

January 22, 1999 -- Vol. 3 Number 4

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Our biology has made us into creatures who are constantly
recreating our psychic and material environments, and whose
individual lives are the outcomes of an extraordinary
multiplicity of intersecting causal pathways. Thus, it is
our biology that makes us free.
-- Richard Lewontin

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Contents of This Issue:

1. On the Patenting of Gene Fragments
2. Astrophysics: On Accelerating Cosmic Expansion
3. On Paleo-Indian Large Mammal Hunters in North America
4. Stretched DNA: A Pauling-Like Structure
5. Zebrafish and Vertebrate Genome Evolution
6. Aneuploidy and Genetic Instability of Cancer Cells

Following the main text: Notices, subscription information,
editorial contacts, etc.

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1. ON THE PATENTING OF GENE FRAGMENTS
In this context, a "clone" is a nucleic acid sequence that is
inserted by some means into the genome of a host so that the new
host genome can then replicate the original sequence in high
quantity. The term "gene library" refers to a collection of DNA
fragments resulting from laboratory digestion of a genome by a
suitable enzyme. Each DNA fragment can then be cloned in
quantity. Libraries of *complimentary DNA (cDNA) are libraries of
those genes currently operational (active) in a living system or
living cell or tissue. An "expressed sequence tag" is a partial
sequence of a clone picked at random from a cDNA library and used
in the identification of genes being expressed in a particular
tissue. The expressed sequence tag technique exploits automated
DNA sequencing and sequence data handling, and a high number of
expressed sequence tags have been found to be associated with
previously unknown genes, which are identified by the predicted
primary protein structure apparently encoded by the gene and the
relation of these proteins to proteins of known structure.
Expressed sequence tags have proved valuable in mapping the human
genome, and there is controversy about attempts to patent such
fragments. ... ... Tony Reichhardt (*Nature*, UK) reports on the
current debate concerning the patenting of gene fragments, the
author making the following points: 1) The recent award of the
first US patent for expressed sequence tags has led to
speculation that similar rights might soon be granted for gene
fragments whose patents have been pending for years. The recent
patent award occurred in October to Incyte Pharmaceuticals (Palo
Alto, CA US), the patent granted for one full-length gene and
polynucleotides that encode more than 40 *protein kinases. 2)
There is apparent disagreement between the US National Institutes
of Health (NIH) and the US Patent Office concerning the patenting
of gene fragments. Although NIH has expressed concern about the
granting of proprietary rights to gene fragments, the US Patent
Office appears poised to grant such rights, and the office
evidently now has applications covering millions of expressed
sequence tags. 3) Last week, at a meeting on intellectual
property rights at the US National Academy of Sciences, Francis
Collins, head of the NIH National Human Genome Research
Institute, called the Incyte patent award a "disturbing turn of
events" and expressed the fear that it signalled the willingness
of the US Patent Office to grant overly broad proprietary rights.
4) Meanwhile, the European Union has published a directive to be
implemented by the year 2000, the directive allowing patents on
isolated human genes and gene fragments with known functions, as
well as on *transgenic life.
-----------
Tony Reichhardt: Patent on gene fragment sends researchers a
mixed message...
(Nature 10 Dec 98 396:499)
QY: Tony Reichhardt 
-----------
Text Notes:
... ... *complimentary DNA (cDNA): Complementary DNA, denoted as
cDNA, is DNA that is synthesized in vitro from an RNA template
using the enzyme reverse transcriptase, and it can be used in
cloning to investigate the presence of various genes, or as a
probe for homologous sequences in various tissues or species.
Essentially, the idea is that if the RNA template is active RNA
in a particular cell type, then the cDNA derived from that RNA
can demarcate the active (operational) genes in that cell type --
the original genes that produced the active RNA.
... ... *protein kinases: In biochemistry, a kinase is an enzyme
that catalyzes a reaction involving the transfer of phosphate
groups, the transfer usually activating another enzyme involved
in a specific function.
... ... *transgenic life: A transgenic organism is an organism
into which genetic material from another organism has been 
transferred, the transferred and incorporated new genes then 
being expressed with the resultant production of specific
proteins.
-------------------
Summary & Notes by SCIENCE-WEEK  22Jan99
-------------------
Related Background:
ON THE ADVANTAGES OF DNA PATENTING
In the international community of molecular biologists, a debate
has been underway for some time concerning the patenting of DNA.
Now John J. Doll (US Government), Director of Biotechnology
Examination at the US Patent and Trademark Office presents the
following points concerning this issue: 1) Just as the issuing of
broad product claims at the early stages of polymer technology
did not deter development of other new vulcanizable copolymers,
the issuing of relatively broad claims in genomic technology
should not deter inventions in genomics. 2) The same patent-
ability analysis is conducted for every patent application,
regardless of whether the application is for a computer chip, a
mechanical apparatus, a pharmaceutical, or a piece of DNA. In
every field of technology -- whether emerging, complex, or
competitive -- all the conditions for patentability (such as
statutory subject matter utility, enablement, written descript-
ion, novelty, and non-obviousness) must be met before a claim is
allowed. 3) In order for DNA sequences to be distinguished from
their naturally occurring counterparts, which cannot be patented,
the patent application must state that the invention has been
purified or isolated or is part of a recombinant molecule or is
now part of a vector. 4) Once a product is patented, that patent
extends to any use, even those that have not been disclosed in
the patent. A future non-obvious method of using that product may
be patentable, but the first patent will be dominant and a
license for the use of the product may be required. 5) Without
the incentive of patents, there would be less investment in DNA
research, and scientists might not disclose their new DNA
products to the public. It is only with the patenting of DNA
technology that some companies, particularly small ones, can
raise sufficient venture capital to bring beneficial products to
the marketplace or fund further research. 6) A strong US patent
system is critical for the continued development and dissem-
ination to the public of information on DNA sequence elements.
QY: John J. Doll, Technology Center 1600, USPTO, Washington, DC
20231 US.
(Science 1 May 98 280:689) (Science-Week 22 May 98)
-------------------
Related Background:
A CAUTION AGAINST DNA PATENTING
In a lengthy and detailed essay, Heller and Eisenberg (University
of Michigan Law School, US) consider the question of whether
patents, particularly biotechnology patents, can deter
innovation. The authors refer to the "tragedy of the commons"
idea first proposed by Garrett Hardin 30 years ago: people often
overuse resources they own in common because they have no
incentive to conserve. Heller and Eisenberg propose that the
recent proliferation of intellectual property rights in
biomedical research suggests a different tragedy, an
"anticommons" tragedy in which people underuse scarce resources
because too many owners can block each other. The authors suggest
that privatization of biomedical research must be more carefully
deployed to sustain both upstream research and downstream product
development, otherwise more intellectual property rights may lead
paradoxically to fewer useful products for improving human
health. In particular, the authors point out that "upstream
patent rights, initially offered to help attract further private
investment, are increasingly regarded as entitlements by those
who do research with public funds. A researcher who may have felt
entitled to coauthorship or a citation in an earlier era may now
feel entitled to be a coinventor on a patent or to receive a
royalty under a material transfer agreement. The result has been
a spiral of overlapping patent claims in the hands of different
owners, reaching ever further upstream in the course of
biomedical research."
QY: Michael A. Heller 
(Science 1 May 98 280:698) (Science-Week 22 May 98)
-------------------
Related Background:
RESEARCHERS SAY DNA PATENTING WILL IMPEDE MEDICAL PROGRESS
Complementary DNA, denoted as cDNA, is DNA that is synthesized in
vitro from an RNA template using the enzyme reverse transcript-
ase, and it can be used in cloning to investigate the presence of
various genes, or as a probe for homologous sequences in various
tissues or species. ... ... Glasner and Rothman (University of
West England Bristol, UK), in a letter to the journal Nature,
tabulate results of a survey of the Human Genome Mapping Project
resource center as an indication of the views of laboratory bench
scientists concerning the legal protection of biotechnological
inventions. This was a UK survey, with 525 respondents, nearly
90% of them located in the UK. Of those surveyed, 86.8% of 508
respondents believe that patenting of partial and uncharacterized
complementary DNA sequences without a knowledge of their
biological function will impede future development of medical
diagnostics and therapeutics.
QY: Harry Rothman 
(Nature 26 Mar 98) (Science-Week 10 Apr 98)
-------------------
Related Background:
GENOME PATENTING: THE MERCK EXCEPTION
In the arena of science, a discovery presupposes the preexistence
of something and implies a finding rather than a making, whereas
an invention implies fabricating something useful as the result
of original thought or experiment. In the arena of law, however,
the differences between discovery and invention are often not so
clear. A rather heated and significant debate, for example, has
arisen in recent years concerning the awarding of patents by the
US Patent Office for bits and pieces of the human genome --
certainly found (discovered) material rather than "invented"
material -- the policy ostensibly in place to provide incentive
for commercial biotechnology research, but also providing as a
consequence various proprietary blockades to access of research
material and research data, the blockades being found onerous and
antithetical to the spirit of science by many researchers.
Biotechnology is an infant discipline, and the legal structure
surrounding it is in process of evolution. That much said, it
should also be said that no one is in apparent agreement on
either side about exactly how that evolution should develop.
Recently, a representative of Merck & Co., one of the major
commercial interests in biotechnology research, outlined
Merck's position in a letter in response to a previous published
report on the human genome patenting problem. Merck's position is
apparently that human genome patenting and researcher access to
materials and data are not mutually exclusive, an attitude
supported by many people in biotechnology. But also in the letter
is the following: "Merck does not believe that patents should be
awarded to either genes or expressed sequence tags for which the
function or utility is purely speculative." Which is consistent
with classical US patent law, but which is not entirely
consistent with the attitudes of many commercial and university
research laboratories that hurry to file patents on bits and
pieces of the human genome whose function is indeed not yet
clarified.
QY: Alan R. Williamson, Merck Research Labs., Merck & Co. Inc.,
Rahway, NJ 07065-0900 US
(Science 31 Oct 97) (Science-Week 21 Nov 97)
-------------------
Related Background:
CONTINUING PROBLEMS OF GENOME PATENTING
The U.S. decision in the 1980s to allow anyone to obtain patent
rights to parts of the human genome is producing fruits these
days that many biologists are calling rotten. Of concern now are
genetic markers called "single nucleotide polymorphisms". A DNA
polymorphism is a DNA sequence that occurs in the population in
two or more variants, each with a significant frequency of more
than abut 1%. A single nucleotide polymorphism is an alteration
occurring in a single nucleotide base, and the alteration may or
may not be involved in a disease process. What is significant in
this context is that these alterations can be used as markers by
researchers scanning an entire genome for significant mutations.
Many researchers consider single nucleotide polymorphisms so
obvious scientifically that they should not be patentable. But
that is not the current situation, and there is concern that the
U.S. Patent Office is handing out patents in molecular biology
without much understanding of the science involved, the ostens-
ible purpose that of promoting commercial funding of potentially
useful health applications. Most biotechnology companies are
exceedingly happy about this attitude. Abbot Laboratories, for
example, has now announced it will invest up to US$20 million of
equity in a company called Genset (Paris, FR), and support up to
US$22.5 million in research for the purpose of acquiring
proprietary rights to as many single nucleotide markers as
possible. Researchers are concerned that commercial entities will
tie up so many parts of the human genome with patents (there are
about 100,000 genes in the human genome) that no one will be able
to do any substantive research on the human genome without paying
royalties to someone.
(Science 19 Sep 97) (Science-Week 10 Oct 97)
-------------------
Related Background:
STATISTICS ON U.S. PUBLIC SECTOR PATENTS ON HUMAN DNA
In a correspondence, S. M. Thomas et al (two installations in the
UK) present results of an analysis of patents published in 1995
that include claims for human DNA sequences. 40% of the patents
are from public-sector institutions such as universities, and
most of them from the U.S. This is double the estimate for the
previous decade. The authors call the increase "remarkable".
(Nature 21 Aug 97) (Science-Week 29 Aug 97)
-------------------
Related Background:
SCIENTISTS URGE CAUTION IN AWARDING OF HUMAN GENE PATENTS
Continuing the expression of concern about the manner in which
current U.S. intellectual property laws may interfere with
scientific research, the U.S. National Academy of Sciences has
joined the National Institutes of Health and the Human Genome
Organization in protesting an interpretation of current patent
law that would permit the issuing of patents on what are called
"expressed gene sequence tags". Bruce Alberts, president of the
National Academy of Sciences, warns against "patents that allow
an early group of inventors who have disclosed little new
knowledge to constrain the actions of subsequent investigators."
(Nature 26 Jun 97) (Science-Week 3 Jul 97)
-------------------
Related Background:
COMPANY OBTAINS PATENT FOR SKIN CANCER MELANOMA GENE
Under present U.S. and European patent law it is possible to
obtain a patent on a human gene in the same manner as one
obtains a patent on a chemical compound. Myriad Genetics, the
Salt Lake City company that has two patents pending for breast
cancer genes (BRCA-1 and BRCA-2), has now received a patent for
the gene it claims causes melanoma (Multiple Tumor Suppressor 1
or MTS1), and for the method of testing for the presence of that
gene in humans. Lisa Cannon-Albright, a University of Utah
geneticist, Mark Skolnik, a Myriad geneticist, and Alexander
Kamb, a Myriad molecular biologist are listed as the inventors.
(New York Times 5 May 97) (Science-Week 8 May 97)


2. ASTROPHYSICS: ON ACCELERATING COSMIC EXPANSION
The idea of cosmic expansion derives from the observation that
radiation from distant galaxies is *redshifted, and the consensus
is that the distance between clusters of galaxies is continuously
increasing, with all galaxies beyond the Local Group apparently
receding from us [*Note #1]. In other words, the Universe as a
whole is expanding, a phenomenon discovered by Edwin Hubble in
1929 but previously suggested by several theoretical cosmologists
(e.g., A. Friedmann [1922], G. Lemaitre [1927]). This expansion
is the observational basis of the *Big Bang theory. Essential to
the study of cosmic expansion is the accurate measurement of
intergalactic distances, and such measurement is dependent on the
use of "standard candles", astronomical objects whose intrinsic
brightness is known and whose distance can therefore be
calculated from apparent brightness. ... ... C.J. Hogan et al (3
authors at 3 installations, US CL) present a review of current
research on the temporal history of cosmic expansion, with
emphasis on recent work concerning the use of *type 1a supernovae
as standard candles. The authors make the following points: 1)
Until recently, the intrinsic brightness of all standard candles
used in observations has been found to be too variable, changing
with the evolution of the object or showing too much diversity
from one object to the other. However, during the past decade,
astrophysicists have been able to precisely determine the
intrinsic brightness of one kind of astronomical object, the type
1a supernova, and these objects have become the best calibrated
standard candles known to astronomers. Currently, observations of
type 1a supernovae are challenging decades of conventional ideas
concerning cosmic expansion. 2) Locating distant supernovae
involves taking images of the same part of the sky a few weeks
apart and searching for changes that might be exploding stars.
Because the digital light detectors can precisely count the
number of photons in each picture element, one makes a simple
subtraction of the first image from the second and looks for
significant differences from zero. With present equipment,
thousands of galaxies are checked in each image pair... After
supernovae candidates are located, the *Keck telescopes in
Hawaii, the largest optical instruments in the world, are pointed
at the objects, and critical observations establish whether or
not the objects discovered are in fact type 1a supernovae. The
observations are then used to gauge the intrinsic brightness of
the objects more exactly and to determine their redshifts... Two
teams have now studied a total of approximately 40 high redshift
supernovae, objects that erupted between 4 and 7 billion years
ago, when the universe was between one-half and two-thirds of its
present age. The results have been surprising: the supernovae are
fainter than expected. The difference is slight, the distant
supernovae on average only 25 percent dimmer than forecast, but
this result is enough to call long-standing cosmological theories
into question. The conclusion from the observations is that the
cosmic expansion is slowing less quickly than previously thought.
3) If the Universe is made of normal matter, gravity must
steadily slow the cosmic expansion. A reduced slowing, as
indicated by the supernovae measurements, implies that the
overall density of matter in the Universe is low... However, the
big surprise is that the observed supernovae are fainter than
predicted even for a nearly empty universe. Taken at face value,
the observations appear to require that expansion is actually
accelerating with time. This is consistent with the "vacuum
energy" embodied in Einstein's equations as the so-called
"*cosmological constant". Unlike ordinary forms of mass and
energy, the vacuum energy adds gravity that is repulsive and can
drive the Universe apart at ever increasing speeds. The authors
conclude: "Evidence for a strange form of energy imparting a
repulsive gravitational force is the most interesting result we
could have hoped for, yet it is so astonishing that we and others
remain suitably skeptical."
-----------
C.J. Hogan et al: Surveying space-time with supernovae.
(Scientific American January 1999)
QY: Craig J. Hogan, Univ. of Washington Seattle 206-543-8992.
-----------
Text Notes:
... ... *redshifted: Redshift (symbol: z) is a lengthening of the
wavelengths of electromagnetic radiation from a source caused
either by the movement of the source (Doppler effect) or by the
expansion of the universe (cosmological redshift). Redshift is
defined as the change in wavelength of a particular spectral line
divided by the unshifted wavelength of that line. Large redshifts
imply large radial velocities (which imply large distances,
according to current cosmological theory), but at redshifts
greater than about 0.2 there is a relativistic divergence from a
linear relation. A redshift of 4.0 corresponds to an object
receding with a radial velocity 92% that of the velocity of
light. The largest astrophysical redshifts so far observed are of
the order of z = 4.9.
... ... *Note #1: In the expansion model, it is the space between
widely separated objects that is expanding. Neighboring objects,
such as close pairs of galaxies, do not move apart because their
mutual gravitational attraction exceeds the effect of the
cosmological expansion. However, the distance between two widely
separated galaxies, or clusters of galaxies, will increase as the
Universe expands.
... ... *Big Bang theory: The Big Bang theory is the general
cosmological model that proposes that all matter and radiation in
the universe originated in an explosion at a finite time in the
past.
... ... *type 1a supernovae: Type 1a supernovae are believed to
be *white dwarf stars that have accreted enough matter from
another star to be pushed over a mass threshold and into a
thermonuclear explosion.
... ... *white dwarf star: White dwarf stars are extremely dense
and compact stars that have undergone gravitational collapse.
They are the final stage in the evolution of low-mass stars after
they have lost their outer layers. White dwarf stars are about
the size of Earth, but with a mass about that of the Sun.
... ... *Keck telescopes: The Keck telescopes are a pair of twin
telescopes at the W. M. Keck Observatory on Mauna Kea, HI US,
each with 10 meter mirrors, the pair constructed 1992-1996. The
installation is managed by the University of California (US) and
the California Institute of Technology (US).
... ... *cosmological constant: A mathematical term introduced by
Einstein into the equations of general relativity, the purpose to
obtain a solution of the equations corresponding to a "static
universe". The term describes a pressure (if positive) or a
tension (if negative) which can cause the Universe to expand or
contract even in the absence of any matter ("vacuum energy").
When the expansion of the Universe was discovered, Einstein
apparently began to regard the introduction of this term as a
mistake, and he described the cosmological constant as the
"greatest mistake of my life". But the term has reappeared as the
proposed source of apparent accelerated cosmic expansion.
-------------------
Summary & Notes by SCIENCE-WEEK  22Jan99
-------------------
Related Background:
ASTROPHYSICS: SUPERNOVAE AND GAMMA RAY BURSTS
Supernovae are violent explosions marking the terminal stage of
certain stars. They are classified into two broad types, Type I
and Type II. A Type II supernova shows hydrogen in its spectrum,
while a Type I supernova shows no hydrogen in its spectrum. Type
I supernovae are further classified as Type 1a, Type 1b, and Type
Ic. A Type 1a supernova is believed to be due to the explosion of
a *white dwarf star in a binary star system, the result of matter
falling onto it from the companion star. When the mass of the
white dwarf exceeds the *Chandrasekhar limit, the white dwarf
undergoes runaway carbon burning and explodes. Type Ib and Ic
supernovae are thought to result from the collapse of the cores
of massive stars which have lost their hydrogen envelopes. Type
II supernovae arise from the explosion of stars of more than 8
solar masses. In this case, the explosion involves a violent
blow-off of outer-layer material after the massive star has
collapsed into a *neutron star or a black hole. Despite the
existing classification scheme, Type Ib and Type Ic supernovae
are more closely related to Type II supernovae than to Type Ia
supernovae. Gamma ray bursts are intense flashes of *gamma rays
detected at energies up to 10^(6) *electronvolts. They were
discovered by US Air Force satellites in 1967 but not
declassified until 1973. The detection of these bursts averages
about 1 per day, and measurements indicate the distribution of
bursts is isotropic, i.e., they are uniformly distributed across
the sky. The current consensus is that gamma ray bursts are
produced by the merger of two neutron stars, and up to this
point, the bursts that have been noted apparently originate
outside our own galaxy. ... ... In 3 contiguous reports in the
same journal, 3 research teams now report an association of the
gamma ray burst of 25 April 1998 (GRB980425) with the supernova
SN1998bw, which exploded at approximately the same time as the
gamma ray burst. Although in general the properties of supernovae
are very different from those of gamma ray bursts, the apparent
new consensus is that supernova SN1998bw establishes a second
class of gamma ray burst which is distinctly different from the
cosmological kind. It is suggested that in some supernovae the
outer layer of the exploding star is given sufficient energy to
cause it to expand at speeds approaching the speed of light, and
that this initially produces a burst of gamma rays and a
subsequent radio emission. If this suggestion is correct, gamma
ray bursts may be produced by two substantially different
mechanisms. [Editor's note: A collection of previous SW reports
on gamma ray bursts can be found in the SW Focus Report
"Astrophysics: Gamma Ray Bursts" which is available at URL
]
-----------
S.R. Kulkarni et al (9 authors at 5 installations, US AU)
Radio emission from the unusual supernova 1998bw and its
association with the gamma-ray burst of 25 April 1998.
(Nature 15 Oct 98 395:663)
QY: S.R. Kulkarni 
-----------
T.J. Galama et al (50 authors at 21 installations, NL US CL IT JP
UK DE AU)
An unusual supernova in the error box of the gamma-ray burst of
25 April 1998.
(Nature 15 Oct 98 395:670)
QY: T.J. Galama 
-----------
K. Iwamoto et al (27 authors at 9 installations, JP IT CL DE NL
US)
A hypernova model for the supernova associated with the gamma-ray
burst of 25 April 1998.
(Nature 15 Oct 98 395:672)
QY: K. Nomoto 
-----------
Text Notes:
... ... *white dwarf star: See previous report.
... ... *Chandrasekhar limit: The remnant mass after the blow-off
during the terminal stage of the life of a star determines the
ultimate fate of the star. If the remnant mass is less than 1.44
solar masses (the Chandrasekhar limit for a star with no hydrogen
content), the star collapses into a white dwarf. If the remnant
mass is greater than 1.44 solar masses, depending on the remnant
mass, the star collapses into either a neutron star or a black
hole. Named after Subrahmanyan Chandrasekhar (1910-1995), who
first proposed the modern theory of stellar gravitational
collapse, and who received the Nobel Prize in Physics 1983.
... ... *neutron star: If, following its terminal stages, the
remnant mass of a star is between 1.4 and 2 to 3 solar masses,
the star will collapse into a neutron star, a body with a radius
of 10 to 15 kilometers, with a core so dense that its component
protons and electrons have merged into neutrons. The average
density of a neutron star is 10^(15) grams per cubic centimeter,
and the weight of an object on the surface of a neutron star
would be 10^(11) its weight on the surface of the Earth. Neutron
stars apparently have an outer shell of iron, but it is iron like
no Earth iron, an iron of 4 orders of magnitude greater density. 
... ... *gamma rays: Gamma rays are radiation of high energy,
from about 10^(5) electronvolts to more than 10^(14)
electronvolts -- radiation with the shortest wavelengths and
highest frequencies, the gamma ray region of the electromagnetic
spectrum merging into the adjacent lower energy x-ray region.
... ... *electronvolts: (eV) A unit of energy defined as the
energy acquired by an electron in falling through a potential
difference of 1 volt. 1 electronvolt = 1.602 x 10^(-19) joule.
-------------------
Summary & Notes by SCIENCE-WEEK  30Oct98
-------------------
Related Background:
RED GIANT STARS AND CONSTRAINTS ON THE HUBBLE CONSTANT
In cosmology, according to the Hubble law that describes the
expansion of the Universe, a law first proposed by Edwin Hubble
in 1929, the apparent recession velocity of galaxies is
proportional to their distance from the observer, with the
proportionality factor denoted as H(sub0). This proportionality
factor is called the "Hubble constant", but in the *Big Bang
theory it varies with time and is really a parameter rather than
a constant. This important cosmological parameter is usually
measured in units of kilometers per second per megaparsec, which
is identified dimensionally as a variation of velocity with
distance. Assuming the Big Bang origin of the expansion, the
"Hubble time" is defined as the reciprocal of the Hubble
constant, and is the time required for the Universe to expand to
its present state, assuming the Hubble constant has remained
unchanged since the Big Bang. Determination of the Hubble time
has been far from unequivocal, with estimates of the Hubble time
ranging between 9 and 18 billion years, depending on various
measurements, models, assumptions, and so on. In the standard Big
Bang theory, the actual age of the Universe is always less than
the Hubble time, because the expansion was faster in the past.
... ... W.E. Harris et al now present a report of observations of
the brightest *red-giant stars in a *Virgo-cluster galaxy, and
the use of these observations to determine constraints on the
Hubble constant. The authors make the following points: 1) The
nearest large groups of *elliptical galaxies (in the Virgo and
*Fornax clusters) play a central role in determinations of the
Hubble constant, and hence the cosmological rate of expansion.
Because the relative distances between these two clusters and
more remote clusters are well known, absolute distance
determinations to Virgo and Fornax should establish the Hubble
constant for the local universe. 2) In addition, elliptical
galaxies reside predominantly in the cores of galactic clusters,
so distance calibrations for ellipticals should minimize the
uncertainties due to the possibly large extent of the clusters
along the line of sight. 3) The authors suggest that a powerful
and direct way of establishing such distances is to use the
brightest red-giant stars, which have nearly uniform
luminosities. 4) The authors report the direct observation of old
red-giant stars in a *dwarf elliptical galaxy in the Virgo
cluster. They determine a distance to this galaxy, and thus to
the core of the Virgo cluster, of 15 megaparsecs, from which they
estimate a Hubble constant of H(sub0) = 77 +- 8 kilometers per
second per megaparsec. Under assumptions of a *low density
Universe with the simplest cosmology, the authors suggest the age
of the Universe is no more than 12 to 13 billion years.
-----------
W.E. Harris et al (4 authors at 4 installations, CA US):
Constraints on the Hubble constant from observations of the
brightest red-giant stars in a Virgo-cluster galaxy.
(Nature 3 Sep 98 395:45)
QY: William E. Harris 
-----------
Text Notes:
... ... *Big Bang theory: See above.
... ... *red-giant stars: A red giant star is a star in a late
stage of evolution, having exhausted the hydrogen fuel in its
core. It has a surface temperature of less than 4700 degrees
Kelvin and a diameter 10 to 100 times that of the Sun.
... ... *Virgo-cluster galaxy: The Virgo cluster is a giant
irregular cluster of galaxies in the constellation Virgo. It is
the nearest large cluster, and approximately 2500 galaxies have
been identified in it.
... ... *elliptical galaxies: These are galaxies that have no
disc component, the shape varying from almost circular to narrow
ellipses. The stars within elliptical galaxies are predominantly
old stars. Elliptical galaxies display the greatest variation in
mass, ranging down to extreme dwarfs (approximately 10^(6) solar-
masses.
... ... *Fornax: The Fornax system is a dwarf elliptical galaxy
in the Fornax constellation. 
... ... *dwarf elliptical galaxy:  A dwarf galaxy is one that is
unusually faint because of small size or low surface brightness
or both. Dwarf galaxies contain only a few million stars, and
they are usually difficult to observe against foreground stars
because they are almost completely transparent. Dwarf galaxies
apparently make up the bulk of the cosmic population.
... ... *low density Universe: The apparent mean density of
matter in the Universe, as determined from both theory and
observation, is a critical parameter that constrains the geometry
and future history of the Universe, and also the age of the
Universe.
-------------------
Summary & Notes by SCIENCE-WEEK  25Sep98
-------------------
-------------------
Related Background:
COSMOLOGY: THE END OF THE OLD MODEL UNIVERSE
Cosmologists are apparently expecting the near-future necessity
for profound conceptual alterations in their field. Peter Coles
(University of London, UK) presents a short review of the current
situation and makes the following points: 1) Observations only
recently made possible by improvements in astronomical
instrumentation have put theoretical models of the Universe under
intense pressure. The standard ideas of the 1980s about the shape
and history of the Universe have now been abandoned -- and
cosmologists are now taking seriously the possibility that the
Universe is pervaded by some sort of "vacuum energy" whose origin
is not at all understood. 2) The weakness of the Big Bang model
is that the numerical values of certain essential parameters in
the model (the Hubble constant, the density parameter, and, in
some versions, the cosmological constant) are not predicted by
theory, and thus the parameters must be inferred from
observations. 3) The Big Bang model does not deserve to be called
a "theory" unless and until it can explain how nonuniformities of
galaxies and clusters of galaxies came into being and evolved. 4)
The Cold Dark Matter model of structure formation, first proposed
in the 1980s, is in serious difficulty because the consequent
significant gravitational brake on expansion is not evident, and
in fact expansion may be accelerating. Current observations
coupled with current dynamical arguments all suggest a global
density of matter in the Universe less than the value required to
make the Universe recollapse. 5) The existence of a cosmological
constant (or vacuum energy) of the required size necessary to
make the basic cosmological models work is not at all explained
by current theories of the fundamental interactions of matter. 6)
There is every reason to be confident that the important issues
will soon be resolved, because a data explosion is about to
engulf cosmology, a new generation of galaxy surveys. The Sloan
Digital Sky Survey, for example, will encompass more than a
million galaxies. The cosmological community is bracing itself
for the arrival of these enormous new data sets and the new
insights they will surely bring. 7) It is possible that none of
the available models will fit all the new data. Coles concludes:
"For many of us, that is the most exciting possibility of all, as
we would have to move to stranger theories, perhaps not even
based on General Relativity."
QY: Peter Coles 
(Nature 25 Jun 98 393:741) (Science-Week 17 Jul 98)
-------------------
Related Background:
EVOLUTION OF COSMIC STRUCTURE: LARGEST SIMULATION TO DATE
One of the important problems in cosmology is to explain the
present structure of the universe, and the evolution of that
structure from the primordial material that came into existence
following the Big Bang. Computer simulations are a significant
part of this research, the idea essentially to calculate from
first principles the properties of a model based on a particular
set of assumptions, compare the results of the calculations with
what is observed in the real universe, and thus, temporarily,
confirm or deny the usefulness of the assumptions that form the
basis of the model. This is the paradigm for most theoretical
model construction in all the sciences, and as a method it is
nothing unique to cosmology. In cosmology, however, the number of
interacting entities is enormous. A new simulation effort was
recently reported, evidently the largest simulation of cosmic
structure to date, the new effort involving consideration of a
simulated cosmos of a billion entities, each of which is
equivalent to about 10 galaxies. The work was carried out at the
Max Planck Institute for Astrophysics (Garching, DE), using a
512-processor Cray supercomputer, and reported at the end of last
month at a cosmology meeting in Paris by Jorg Colberg (MPI-
Astrophysics Garching, DE). The work was also presented a week
ago at the American Astronomical Society San Diego (US) meeting
by August Evrard (University of Michigan, US). This is apparently
the first simulation of how gravity could have gathered post-Big
Bang ripples into large meta-galactic structures -- walls,
clumps, filaments of galaxies -- filling all of space. Some
astrophysicists are saying this work marks a turning point in
numerical cosmology, and they expect this model universe to be a
powerful tool for interpreting data from large surveys of the
real sky. This simulation omits factors other than gravity, such
as pressure and radiation, that also govern galaxy formation. The
calculations have involved two different models, one a model
based on a mass density sufficient to stop cosmic expansion, and
the other (called the "lambda" model) based on a light-mass
universe that will expand forever. Apparently, it is the lambda
model that is producing structures more in agreement with
observations, although both models have difficulty accounting for
some of the more massive and distant galaxy clusters seen in the
real sky.
QY: Joseph Glanz (science_editors@aaas.org)
(Science 5 Jun 98 280:1522) (Science-Week 26 Jun 98)
-------------------
Related Background:
AN ARGUMENT FOR A LIGHTWEIGHT UNIVERSE
As mentioned in the previous report, a fundamental question in
cosmology is whether the expansion of the universe will continue
indefinitely (an open universe) or eventually cease (a closed
universe). According to the current analytical framework used to
describe the universe, the answer to this question depends on the
mass density of the universe. If the mass density is below a
certain calculated value, the "critical density", there is not
enough mass to provide the gravitational attractions necessary to
slow and halt the expansion. This critical density is equal to
1.9 x 10^(-29)H^(2) grams per cubic centimeter, which is
equivalent to approximately 10 protons per cubic meter. The (H)
indicated is the Hubble constant, the rate at which the expansion
velocity of the universe changes with distance. Often used is a
derived constant Omega(sub m), which is expressed in units of the
critical density, so that a value of Omega(sub m) = 1 means the
mass density is the critical density. The standard models of the
initial expansion of the universe (*inflation), as well as
general arguments not dependent on ad hoc adjustments of
cosmological parameters, predict a flat universe with the
critical density needed to just halt its expansion. But at the
present time, only a small fraction of the critical density has
been detected, even when all the unseen dark matter in galaxy
halos and clusters of galaxies is included. There is apparently
no reliable indication that most of the matter needed for closing
the universe does in fact exist. ... ... Bahcall and Fan
(Princeton University, US) present an analysis of the problem of
cosmic mass density. They propose that several independent
measures, especially those using the largest bound systems known
-- clusters of galaxies -- all indicate that the mass density of
the universe is insufficient to halt the expansion. They also
propose that a new method involving the evolution of the number
density of clusters with time provides the most powerful
indication so far that the universe has a subcritical density.
The authors suggest that various techniques reveal a consistent
picture of a lightweight universe with only 20 to 30 percent of
the critical density, and thus the universe may expand forever.
QY: Neta A. Bahcall 
(Proc. Natl. Acad. Sci. US 26 May 98 95:5956)
(Science-Week 26 Jun 98)
-----------
Text Notes:
... ... *inflation: The inflationary model, first proposed by
Alan Guth in 1980, involves the idea that quantum fluctuations in
the time period 10^(-35) to 10^(-32) seconds following the
Big Bang were quickly amplified into large density variations
during the "inflationary" 10^(50) expansion of the universe in
that time frame.
-------------------
Related Background:
NEW EVIDENCE FOR A COSMIC ANTIGRAVITY FORCE
Type 1a supernovas are believed to be white dwarf stars that have
accreted enough matter from another star to be pushed over a mass
threshold (the Chandresekhar threshold) and into a thermonuclear
explosion. Since most supernovas of this type have similar
spectral emission curves and absolute magnitudes at maximum, they
can be used as "standard candles" for distance determinations,
i.e., their apparent luminosity becomes a measure of their
distance. At a recent astrophysics meeting (3rd International
Symposium on Sources and Detection of Dark Matter in the
Universe, 18-20 February 1998, Marina del Rey, Calif., US),
Alexei Filippenko (University of California Berkeley, US)
presented a report that 14 distant type Ia supernovas are on the
average 10% to 15% further away than expected, and these results,
coupled with previous independent observations by others on other
type 1a supernovas, are pushing astrophysicists to a consensus
that cosmic expansion is accelerating, rather than decelerating
due to gravitational forces, and that a repulsive antigravity
force may be counteracting gravity on large scales. One
theoretical result has been a renewed interest in Einstein's
"cosmological constant", an intrinsic space-time background
energy that would produce such a force, and which for many years
has been disregarded as an ad hoc theoretical improvisation.
Apparently, astrophysicists are all accepting the new supernova
data, and the question is what to make of it -- and whether some
serious theoretical reformulations are necessary.
QY: James Glanz 
(Science 27 Feb 98) (Science-Week 13 Mar 98)
-------------------
Related Background:
COSMOLOGY: OPEN, CLOSED, OR FLAT UNIVERSE?
Marc Kamionkowski (Columbia University, US) reviews current
research in cosmology, making the following points: 1) Determin-
ation of the geometry of the universe has been a central goal of
cosmology ever since Hubble discovered its expansion 75 years
ago. 2) The central question is whether the universe is a multi-
dimensional equivalent of a 2-dimensional surface ("flat"), a
sphere ("closed"), or a saddle ("open"). The geometry, in the
context of current theory and observations, determines whether
the universe will expand forever or eventually collapse. 3) Until
now, most astronomers have pursued the geometry by attempting to
measure the mass density of the universe. According to general
relativity, if the density is equal to, larger than, or smaller
than a critical density fixed by the expansion rate, then the
universe is flat, open, or closed, respectively. 4) Another
possibility is to look directly at the predicted observational
effects of a curved (open or closed) universe versus a flat
universe, and in particular at the angular power spectrum of the
cosmic microwave background. The authors suggest that in the near
future a new generation of experiments will provide substantial
advances in these observations, enabling more definitive
statements about the geometry of the universe, and that these
results will in turn provide clues to the new particle physics
required to understand the inflation phase following the Big Bang
origin of the universe.
QY: Marc Kamionkowski 
(Science 29 May 98 280:1397) (Science-Week 19 Jun 98)
-------------------
Related Background:
A SUPERNOVA EXPLOSION AT HALF THE AGE OF THE UNIVERSE
Redshift (symbol: z) is a lengthening of the wavelengths of
electromagnetic radiation from a source caused either by the
movement of the source (Doppler effect) or by the expansion of
the universe (cosmological redshift). According to current ideas,
the expansion of the universe should be counteracted by gravit-
ational forces, and if the mass of the universe is sufficient,
this gravitational attraction will ultimately cause a cessation
of expansion and the beginning of a sustained gravitational
contraction. If expansion is indeed slowing, the cosmological
redshift should be time-dependent, and an analysis of the
redshift of objects in the ancient universe (by observations of
extremely distant objects) should reveal this slowing of
expansion due to gravitational forces produced by cosmic mass.
Supernovas are stellar explosions of stars with original masses
greater than about 3 solar masses, and type 1a supernovas are
believed to be white dwarf stars that have accreted enough matter
from another star to be pushed over a mass threshold and into a
thermonuclear explosion. S. Perlmutter et al (22 authors at 16
installations, US IT UK FR SE DE CL ES) report the most distant
spectroscopically confirmed supernova, SN1997ap, at an apparent
redshift z = 0.83. Spectra and photometry from the largest
telescopes on the ground and in space indicate this ancient
supernova is similar to nearby recent type Ia supernovas. The
authors suggest that these measurements, when combined with
recent measurements of nearer supernovas, indicate we may live in
a low-mass-density universe.
QY: S. Perlmutter 
(Nature 1 Jan 98) (Science-Week 16 Jan 98)


3. ON PALEO-INDIAN LARGE MAMMAL HUNTERS IN NORTH AMERICA
The time and circumstances surrounding the arrival of the first
human inhabitants of North and South America continues to be
debated. ... ... George C. Frison (University of Wyoming, US)
presents a review of the field, the author making the following
points: 1) From approximately 11,200 to 8,000 years ago, the
Great Plains of North America were populated by small Paleo-
Indian hunting groups with well developed weaponry and the
expertise to successfully hunt large mammals, especially mammoths
and bison. 2) Mammoths became extinct on the Plains by 11,000
years ago, and although paleo-ecological conditions were
worsening, the demise of mammoths may have been hastened by human
predation. 3) After the extinction of mammoths, the main target
of the Plains Paleo-Indian hunters consisted of subspecies of
bison (Bison antiquus and Bison accidentalis). As bison
populations gradually diminished, apparently because of worsening
ecological conditions, by approximately 8,000 years ago, human
subsistence was forced into a greater dependence on small animal
and plant foods. 4) Human paleo-ecology studies of the Paleo-
Indian time period rely heavily on multi-disciplinary efforts.
*Geomorphologists, botanists, soil scientists, *palynologists,
biologists, and other specialists aid archeologists in data
recovery and analysis, although with few exceptions their
contributions are derived from the fringes rather than from the
mainstreams of their disciplines.
-----------
George C. Frison: Paleoindian large mammal hunters on the plains
of North America.
(Proc. Natl. Acad. Sci. US 24 Nov 98 95:14576)
QY: George C. Frison, University of Wyoming 307-766-5160.
-----------
Text Notes:
... ... *Geomorphologists: The study of the origin of secondary
topographic features carved by erosion.
... ... *palynologists: The study of spores, pollen,
microorganisms, and microscopic fragments of megaorganisms in
sediments.
-------------------
Summary & Notes by SCIENCE-WEEK  22Jan99


4. STRETCHED DNA: A PAULING-LIKE STRUCTURE
DNA *supercoiling plays a fundamental role in the biological
cell. In *prokaryotes, *plasmid and genomic DNA is often found to
be slightly underwound, a property apparently required for proper
initiation of replication. In the nuclei of *eukaryotes, DNA is
highly compacted by successive stages of coiling. First, it is
organized in "*nucleosomes" by winding twice around a histone
core. This bead-on-a-string structure of nucleosomes, together
with naked DNA segments, forms "chromatin", which is compacted
further by winding into a solenoidal structure approximately 34
nanometers in diameter. This thick chromatin fiber then may coil
into "*plectonemes", condensing DNA even further. DNA
supercoiling is also generated in processes such as
*transcription and replication, where it is relaxed by the
specific action of a large class of enzymes, the *topoisomerases.
Finally, DNA supercoiling is involved in gene regulation, since
locally unwound DNA is necessary for transcriptional activation
and *recombination repair. ... ... J.F. Allemand et al (4 authors
at 2 installations, FR) report an investigation of structural
transitions within a single stretched and supercoiled DNA
molecule. The technique involves attaching chemical anchors to
each end of the DNA molecule, then chemically fixing one end of
the molecule to an appropriately coated glass surface, and
chemically fixing the other end of the molecule to a magnetic
bead under the influence of a local applied magnetic field [*Note
#1]. The authors report the production of various structural
transitions in the single DNA molecule, one of which is a
transition to a new highly twisted structure with approximately
2.62 bases per turn and an extension 75 percent larger than B-DNA
(the native DNA structure in biological cells). This new highly
twisted structure has a tightly interwound phosphate backbone and
exposed bases in common with the early DNA structure first
proposed by Linus Pauling in 1953 ... ... In a commentary on this
work in the same issue of the journal, Alexander Rich
(Massachusetts Institute of Technology, US) points out that the
study of DNA conformational changes often provides significant
insight into how the molecule functions, and new experimental
techniques involving single DNA molecules are therefore of
considerable interest. Rich concludes: "The field of single-
molecule DNA biochemistry is relatively new. As it matures, we
will understand how forces at the molecular level of the order of
piconewtons underlie the varied chemistries and molecular biology
of genetic material."
-----------
J.F. Allemand et al: Stretched and overwound DNA forms a Pauling-
like structure with exposed bases.
(Proc. Natl. Acad. Sci. US 24 Nov 98 95:14152)
QY: J.F. Allemand 
-----------
Text Notes:
... ... *supercoiling: (coiled-coil) The form of DNA that can be
envisaged as resulting if a double-stranded DNA molecule were
turned through a hairpin bend and the 2 double-stranded rails
twisted one around the other. In general, DNA in vivo is
supercoiled. 
... ... *prokaryotes: Unicellular or filamentous organisms in
which cells lack internal membrane compartments such as a
nucleus (e.g., bacteria).
... ... *plasmid: An extra-chromosomal piece of DNA, often
circular, mostly in bacteria but also in yeast, capable of
independent replication and also capable of translocation to
other organisms of the same or other species.
... ... *eukaryotes: Cells with internal membrane compartments,
e.g., a nucleus.
... ... *nucleosomes: The nucleosome is a tertiary structure of
chromosomal DNA found in eukaryotic cells. In chromosomes, about
every 200 nucleotides, the DNA double helix is coiled around a
complex of 8 histone proteins, the entire assembly having the
appearance of beads on a string. The beads of nucleosomes are in
turn supercoiled into a solenoid structure, and the entire
complex of the eukaryotic chromosome is called "chromatin". The
small histones proteins are basic (as opposed to acidic)
proteins, and they are essential in forming nucleosomes. 
... ... *plectonemes: (plectonemic spiral) In general, a
plectoneme is a spiral in which 2 parallel threads coil in the
same direction about one another and cannot be separated unless
uncoiled. [Concerning the term "parallel": the 2 DNA strands in
the double helix are "anti-parallel" in the chemical sense -- the
strands run in opposite directions vis a vis the sequence of
subunits. The term "parallel" here refers to the plain geometric
sense --  2 strands lying parallel to each other.] Chromatin
coiling is considered to be "loosely plectonemic", and is
sometimes called "relational" coiling.
... ... *transcription: Transcription is the process by which
genetic information in DNA is converted into RNA.
... ... *topoisomerases: Replication of the genome of any cell,
be it prokaryote or eukaryote, involves not only the DNA of the
cell, but also a cluster of enzymes and helper proteins, and the
entire set of entities can be said to be involved in one of the
most elegant molecular ballets found anywhere in nature. In
prokaryotes, such as bacteria, the genome is in the form of a
closed loop of DNA. If this loop is twisted into a supercoil, or
knotted, or catenated, these derivative forms must be altered and
the relaxed open loop restored before replication of the loop can
begin. There are enzymes involved in these processes, and those
that have been identified are called topoisomerases, the topo-
prefix indicating an enzyme that catalyzes topological change.
The ability of topoisomerases to do their work, to alter the
unwanted linked states of DNA, is essential for cell survival,
and this work of untying the knot or knots of a huge looped
double-helical strand (in prokaryotes), or a linear
double-helical strand (in eukaryotes) is quite remarkable. In
brief, what these enzymes, the topoisomerases, do is apparently
first recognize the entire topology of the DNA molecule, the
supercoils, the knots, the catenanes, and then move in to precise
points to cleave and pass and splice so that a relaxed
double-helix of DNA is obtained, linear in eukaryotes and a
closed loop in prokaryotes, all of this a precursor to the main
part of the ballet, the replication process.
... ... *recombination repair: In general, the formation of a 
normal DNA molecule by exchanging correct for incorrect segments
between 2 damaged molecules.
... ... *Note #1: The DNA used in these experiments had
approximately 17,000 bases and was chemically altered at its
extremities with several *biotin and digoxigenin groups. The DNA
molecules were bound at one end to a glass surface coated with
anti-digoxigenin *antibody and at the other end with to a
*streptavidin-coated 4.5 micron magnetic bead. The single DNA
molecule itself was approximately 5 microns in length. The
stretching force was controlled by varying the distance between
the sample and permanent magnets; rotating the magnets induced
DNA supercoiling.
... ... *biotin: Also known as vitamin H. Biotinyl residues bind
strongly to *streptavidin.
... ... *streptavidin: a bacterial protein (from Streptomyces
avidinii) capable of binding up to 4 biotin molecules per
streptavidin molecule.
... ... *digoxigenin: An aglycon of digoxin, the familiar cardio-
active glycoside (Digitalis extract).
... ... *antibody: In general, an antibody is a protein molecule
produced by the immune system of vertebrate organisms, the
molecule designed to specifically interact with a particular
invading foreign entity called an antigen. In the laboratory,
antibodies specific to a variety of substances can be easily
produced in an appropriate experimental animal, and the
antibodies then separated from animal blood and used as binding
agents in biochemical and biophysical experiments. In the
reported experiment, the antibody coating the glass surface acts
as the binder for the digoxigenin end of the DNA molecule.
-------------------
Summary & Notes by SCIENCE-WEEK  22Jan99
-------------------
Related Background:
RESPONSE OF SINGLE DNA MOLECULES TO SUDDEN ELONGATIONAL FLOW
The theoretical study of the dynamics of flexible polymer
molecules in fluid flows has been an active area of research for
more than 60 years. A polymer in elongational flow begins to
deform when the force due to hydrodynamic friction across the
molecule exceeds the *entropic elasticity that tends to coil it.
Physical analysis of the dynamics may lead to an understanding of
the appearance of various polymer conformations. ... ... Smith
and Chu report a study in which individual fluorescence-labeled
*bacteriophage lambda-DNA molecules in sucrose and glucose
solutions were exposed to an elongational flow producing a high
*strain rate, and the dynamics of the molecules recorded with
video fluorescence microscopy. The flow was turned on suddenly so
that the entire evolution of molecular conformation could be
observed without initial perturbations. The rate of stretching of
individual molecules was highly variable and depended on the
molecular conformation that developed during stretching. This
variability is apparently due to a dependence of the dynamics on
the initial random equilibrium conformation of the polymer coil.
The authors suggest the increasing appearance at high strain 
rates of slowly unraveling hairpin folds is an example of
*nonergodic dynamics, which can occur when a statistical
mechanical system is subjected to *nonadiabatic (or "sudden")
external forces. The authors further suggest that nonequilibrium 
statistical mechanics may also play a role in the behavior of
large proteins when a local driving mechanism is faster than the
*relaxation times between different subunits of the protein.
-----------
D.E. Smith and S. Chu (Stanford University, US): Response of
flexible polymers to a sudden elongational flow.
(Science 28 Aug 98 281:1335)
QY: Steven Chu 
-----------
Text Notes:
... ... *entropic elasticity: In this context, elasticity is the
property whereby a molecule changes its shape due to imposed
forces, but recovers its original configuration when the forces
are removed. Entropic elasticity is an elasticity with an
equilibrium configuration governed by thermodynamic entropy
constraints.
... ... *bacteriophage lambda-DNA: Bacteriophage is a virus that
infects bacteria, the virus essentially consisting of a naked
strand of DNA surrounded by a complex polyhedral shell ("capsid")
composed mainly of glycoproteins. Lambda-DNA is DNA from the so-
called lambda type of bacteriophage.
... ... *strain: Strain is the deformation produced in a solid
(here a molecule) as the result of stress (external forces acting
on the system).
... ... *nonergodic dynamics: An ergodic system or process is one
in which averages computed from a data sample over time converge,
i.e., all sizeable data samples are equally representative of the
whole. In general, a dynamical system or process is ergodic if it
tends in probability to a limiting form which is independent of
the initial conditions. Nonergodic dynamics thus refers to
dynamics that never realize a limit independent of initial
conditions.
... ... *nonadiabatic: An adiabatic process is any thermodynamic
process, reversible or irreversible, that takes place in a system
without exchange of heat with the surroundings of the system. All
real processes are nonadiabatic in the sense that some heat
exchange always occurs. But close approximation to an adiabatic
ideal can be realized in practice.
... ... *relaxation times: The relaxation time of a system is a
measure of the time the system requires to return to equilibrium
(or assume a new equilibrium) after a sudden change in applied
forces, constraints, boundary conditions, etc. Also called the
time constant of the system. In a more general sense, the term
"relaxation time" is also used to describe the response time of a
system to any change in conditions.
-------------------
Summary & Notes by SCIENCE-WEEK  18Sep98


5. ZEBRAFISH AND VERTEBRATE GENOME EVOLUTION
To an engineer with open eyes, the assemblage of parts that
constitute a living organism is an engineering marvel. The
exterior anatomy of an insect, for example, involves a complex
arrangement of numerous parts with specific mechanical and
sensory functions, and this assemblage is replicated with great
precision in the production of each generation. In an ordinary
manufacturing plant, the various parts of a machine are usually
manufactured independently of each other and then the finished
parts assembled according to an external grand plan to produce
the final manufactured product. In a biological organism,
however, the "manufacturing" scheme is quite different: In the
first place, the "grand plan" is internal and not external: each
cell of the organism carries the "grand plan" -- the genome --
with specific parts of the plan activated in each cell type, and
the activation/inactivation of specific parts of the genome
differentially dynamic in various cell types during the
developmental process. Secondly, during development of the
embryo, body parts are developed in parallel, in tandem, in
sequence, with an intricate network of control loops, until
finally the complete developed product emerges in toto as a
functioning entity. How is this biological development and
assembly process orchestrated? One of the most spectacular
findings of this decade has been that flies and mice use the same
genes for specifying embryonic developmental regions along the
anterior-posterior axis of the body. In general, "homeotic" genes
are genes that control development, and "homeogenes" are the
subset of homeotic genes that contain "homeoboxes". A "homeobox"
is a part of a gene encoding a protein "homeodomain", a protein
domain that binds to DNA. (The protein functions as one of a
number of "*transcription factors".) The DNA-binding homeodomain
consists of approximately 60 amino acids, and these homeodomain
motifs are apparently involved in orchestrating the development
of a wide range of organisms. "Hox" genes are a subset of
homeogenes, the Hox genes encoding proteins (and protein
homeodomains) that determine positional cell differentiation and
development. Mutations in Hox genes result in the conversion of
one body part into another: for example, in the fruit fly
Drosophila, a specific Hox mutation results in a leg appearing
where an antenna usually appears. There are clusters of Hox genes
in the genome: e.g., 1 Hox cluster in *nematode worms, 2 Hox
clusters in the fruit fly Drosophila, 4 Hox clusters in
vertebrates. Since mammals have more clusters of Hox genes than
lower forms, it has been thought that Hox cluster duplication
facilitated the evolution of the vertebrate body plans.
... ... A. Amores et al (13 authors at 7 installations, US CA)
now report that *zebrafish (Danio verio) have 7 Hox clusters.
Thus, *teleosts, the most species-rich group of vertebrates,
appear to have more copies of these developmental regulatory
genes than do mammals, despite less complexity in the anterior-
posterior axis. The authors report that *phylogenetic analysis
and *genetic mapping suggest a *chromosome doubling event,
probably by whole genome duplication, after the *divergence of
*ray-finned and lobe-finned fishes, but before the teleost
*radiation. The authors state: "The conclusion that the genetic
complexity of Hox clusters in teleost fish has exceeded that of
mammals for more than 100 million years calls into question the
concept of a tight linkage of Hox cluster number and
morphological complexity along the body axis."
-----------
A. Amores et al: Zebrafish Hox clusters and vertebrate genome
evolution.
(Science 27 Nov 98 282:1711)
QY: John H. Postlethwait, Univ. of Oregon Eugene 541-346-1000.
-----------
Text Notes:
... ... *transcription factors: Transcription is the process by
which the genetic information in DNA is converted into RNA, and
transcription factors are a class of DNA-binding proteins that
regulate RNA transcription.
... ... *nematode worms: An abundant and ubiquitous phylum of
unsegmented roundworms.
... ... *zebrafish: A common tropical aquarium species.
... ... *teleosts: In general, this refers to any of the bony
fish, the most advanced in terms of evolution and the largest
group of fish. Besides the calcified internal skeleton, the most
obvious uniform characteristic of the teleost fish is their tail,
with upper and lower halves of about equal size, whereas in
cartilaginous fish the tail has two lobes of unequal size. Almost
all sport, commercial, and ornamental fish are teleosts.
... ... *phylogenetic analysis: In general, an analysis of
evolutionary history.
... ... *genetic mapping: (chromosome mapping; linkage mapping)
In general, elucidation of the linear arrangement of genes on a
*chromosome or of sites within a gene. 
... ... *chromosome: In cells with chromosomes, the
chromosomes are the physical structure into which DNA is
organized and on which genes are carried.
... ... *divergence: In this context, the acquisition of
dissimilar characteristics by related organisms in unlike
environments.
... ... *ray-finned and lobe-finned fishes: Actinopterygii and
Crossopterygii.
... ... *radiation: In this context, the term "radiation" refers
to the spread of a group of biological entities into new
environments with consequent diversification.
-------------------
Summary & Notes by SCIENCE-WEEK  22Jan99
-------------------
Related Background:
A DROSOPHILA HOMOLOG OF RX VERTEBRATE HOMEOBOX GENE
Homeobox genes are a family of similar nucleotide sequences that
encode sequence-specific DNA binding proteins that are essential
for embryological development and cell differentiation. They were
first discovered in the fruit fly Drosophila, but they have
homologs in the genomes of many organisms, including humans and
plants. A homeodomain is a protein motif encoded by a homeobox
DNA sequence, and an {Rx} gene is a vertebrate homeobox gene that
has been linked to the embryological development of the
vertebrate eye. Xenopus is a vertebrate, a species of African
toad. ... ... Eggert et al (5 authors at 2 installations, DE CH)
report the isolation of an Rx gene from Drosophila (called DRx).
The homeodomains of the Drosophila and the Xenopus Rx genes are
identical, suggesting that the Drosophila DRx gene is a homolog
of the vertebrate Rx gene. The Drosophila gene is expressed
during early embryonic development, and later in the brain and
central nervous system, and the sequence conservation and
expression pattern suggest an important role of the gene during
brain development in Drosophila. But no expression of this gene
has been detected in embryological precursor tissue of the eye.
The authors suggest that vertebrate Rx genes might be involved in
brain patterning processes and specification of eye fields in
different phyla.
QY: Uwe Walldorf 
(Proc. Natl. Acad. Sci. US 3 Mar 98) (Science-Week 3 Apr 98)
-------------------
Related Background:
HOMEOBOX GENES AND ECHINODERM EVOLUTION
Echinoderms are members of a phylum of marine invertebrates, and
they include starfish, sea urchins, sea cucumbers, etc. Most
echinoderms exhibit radial symmetry, but the free-swimming larvae
are bilaterally symmetrical before they metamorphose into adults.
The evolution of the dramatic morphological changes evidenced in
echinoderms, which apparently evolved from bilaterally symmetr-
ical forms, is not yet clarified, and the problem is a challenge
to molecular evolutionary biologists. Homeobox is a family of
similar nucleotide sequences that encodes sequence-specific DNA-
binding proteins, and they are apparently essential for the
differentiation of various cell groups during embryonic develop-
ment. Homeobox sequences were first discovered in the fruit fly,
but they have homologues in many organisms, including humans.
Homeodomains are the protein motifs encoded by the homeobox DNA
sequences, these protein motifs apparently binding to DNA and
activating or repressing specific target genes. Christopher J.
Lowe and Gregory A. Wray (State University of New York Stony
Brook, US) report the expression domains in echinoderms of 3
developmental regulatory genes (, ,
), all of which encode transcription factors that
contain a homeodomain, and evidence that evolutionary reorganiz-
ation of body architecture in echinoderms involved extensive
changes in the deployment and roles of homeobox genes. The
authors suggest this demonstrates the evolutionary lability of
regularity genes that are widely viewed as conservative.
QY: G. Wray 
(Nature 16 Oct 97) (Science-Week 14 Nov 97)


6. ANEUPLOIDY AND GENETIC INSTABILITY OF CANCER CELLS
In general, germ cells (egg cells and sperm cells) and somatic
cells (non-germ cells) carry different numbers of chromosomes,
with germ cells carrying exactly half the number (haploid number)
of somatic cell chromosomes (diploid number). The term
"aneuploidy" (heteroploidy) refers to a condition in which the
number of chromosomes in a cell is not an integer multiple of the
haploid number typical for that cell or organism. For example,
the haploid human chromosome number is 23; the normal somatic
cell contains 46 chromosomes; a somatic cell with 47 or 44
chromosomes is aneuploid. Some authors, however, use the term
"aneuploidy" to indicate merely an abnormal number of
chromosomes. In cell biology, the term "karyotype" refers to the
characteristics profile (number, size, and shape) of a set of
chromosomes of a cell or organism. In this context, the term
"phenotype" refers to the total appearance of a cell as
determined by the interaction during development between its
genetic constitution (genotype) and the cell's environment.
Genetic and phenotypic instability are hallmarks of cancer cells,
but the cause of the instability is not clear. The leading
hypothesis suggests that a poorly defined gene mutation generates
genetic instability and that one or more of the many subsequent
mutations then cause cancer [*Note #1]. ... ... P. Duesberg et al
(2 installations, DE US) report an investigation of the
hypothesis that genetic instability of cancer cells is caused by
aneuploidy, which they define as "an abnormal balance of
chromosomes". The authors point out that because symmetrical
segregation of chromosomes during mitosis depends on exactly two
copies of the genes involved in mitosis ("mitosis genes"),
aneuploidy involving chromosomes bearing mitosis genes will
destabilize the karyotype. The authors propose that the
aneuploidy hypothesis predicts that the degree of genetic
instability should be proportional to the degree of aneuploidy,
and it should thus be difficult to maintain the particular
karyotype of a highly aneuploid cancer cell on *clonal
propagation. The authors report this prediction is confirmed with
clonal cultures of chemically transformed aneuploid Chinese
hamster embryo cells. Defining the "ploidy factor" as the
quotient of the modal chromosome number divided by the normal
number of the species, it was found that the higher the ploidy
factor of a clone, the more unstable was its karyotype. The
authors point out that work by others has established an exact
correspondence between the karyotype instability of human colon
cancer cell lines and the degree of aneuploidy. The present
authors suggest that, independent of gene mutation, aneuploidy is
sufficient to explain genetic instability and the resulting
karyotypic and phenotypic heterogeneity of cancer cells. The
authors further suggest that because aneuploidy has also been
proposed to cause cancer, their hypothesis "offers a common,
unique mechanism of altering and simultaneously destabilizing
normal cellular phenotypes."
-----------
P. Duesberg et al: Genetic instability of cancer cells is
proportional to their degree of aneuploidy.
(Proc. Natl. Acad. Sci. US 10 Nov 98 95:13692)
QY: Peter Duesberg 
-----------
Text Notes:
... ... *Note #1: In 1976, Peter Nowell postulated that a
precancerous mutation generates exceptional "genetic instability"
or "mutability", and that the highly mutable "premalignant" cell
then suffers many further gene mutations, including those that
cause cancer (P.C. Nowell, Science 194:21 1976).
... ... *clonal propagation: In general, in this context, a
"clone" is a line of identical cells produced from one or a few
originating cells.
-------------------
Summary & Notes by SCIENCE-WEEK  22Jan99


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