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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.
December 25, 1998 -- Vol. 2 Number 52
The Editors extend to everyone Holiday Greetings
and best wishes for the New Year.
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Dissent is the native activity of the scientist.
-- Jacob Bronowski (1908-1974)
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Contents of This Issue:
1. On the Sharing of Research Tools
2. On the Optical Counterparts of Gamma-Ray Bursts
3. On the Fossil Tracks of Vertebrates
4. Cell Biology: On Asymmetric Cell Division
5. On the Folding of Secretory and Membrane Proteins
6. Evidence for a Factory Model of DNA Replication
7. Reovirus Destruction of Tumors
Letter: On the Origin of the Solar System
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1. ON THE SHARING OF RESEARCH TOOLS
In an unsigned lead editorial on the subject of sharing of
research tools among scientists, the journal *Nature* makes the
following points: 1) Increasingly tough conditions being attached
to the transfer of experimental tools between researchers are
threatening the tradition in science of open communication. 2) In
most areas of physical science, research tools that have been
painstakingly developed cannot be easily reproduced, which means
the researcher who has developed such a tool usually has a
significant head-start on potential competitors. But in much of
biology, tools that are difficult to produce can be trivial to
replicate, which means that sharing research tools has become the
norm among biologists. 3) Currently, however, there is increasing
concern in the biomedical community that some researchers are
prepared to share their materials only when competitive advantage
and prospects of commercialization are not compromised. 4) A bold
stance on any restrictions on shared tools and transferred
materials seems wishful thinking given the growing use of highly
restrictive "materials transfer agreements" by corporations and
universities. Too often, the negotiations of these agreements is
the rate-limiting step in sharing materials. 5) The *Nature*
editorial recommends the adoption of a uniform materials transfer
agreement: "If universities, companies, and funding agencies were
to agree on such a form, journal editors could require that it be
used by their authors. No one need lose but the lawyers."
[Editor's note: In addition to the related background material
below, related briefs can be found in the SCIENCE-WEEK Focus
Report "Science and Commerce in Conflict", available at URL:
.]
----------
Editor (*Nature*)
Sharing research tools is a tradition worth defending.
(Nature 12 Nov 98 396:97)
QY: Editor
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Summary by SCIENCE-WEEK http://scienceweek.com 25Dec98
-------------------
Related Background:
COMMERCIALIZATION AND THE INHIBITION OF SCIENTIFIC EXCHANGE
Relations between research universities and industry are evid-
ently deteriorating, and the cause of the deterioration is
apparently also deteriorating relations between research univ-
ersities themselves. The problem is the commercialization of
scientific research, particularly the increasingly common demand
for control of any publication and patent rights subsequent to
the furnishing of "proprietary" research material. The essential
paradigm is as follows: A scientist at University A requests
research material from a scientist at University B, and Univ-
ersity B requires the University A scientist to sign what is
called a materials transfer agreement that in effect is a con-
tract that says University B retains rights to anything profit-
able that comes out of the related work of scientist A, and that
scientist A must submit research results to University B for
review prior to publication. The legal routine is apparently even
more stringent when interactions between university researchers
and industry researchers are involved. This is a scientific
horror story to any scientist older than 50, all of whom remember
the days when research material was easily requested and freely
given without legal entanglements of any sort. One of the most
outspoken groups criticizing the present system is a group of
biologists at the University of California San Francisco led by
Keith Yamamoto who say prepublication review of manuscripts
"endangers the academic tradition of free and open publication."
Considering that the present dynamic commercialization of science
may totally transform the structure of science, there may be
more than free publication involved.
QY: Keith Yamamoto, Univ. Calif. San Francisco (415) 476-4044
(Science 10 Oct 1997) (Science-Week 31 Oct 97)
2. ON THE OPTICAL COUNTERPARTS OF GAMMA-RAY BURSTS
Gamma rays are radiation of high energy, from about 10^(5)
electronvolts to more than 10^(14) electronvolts -- radiation
with the shortest wavelengths and highest frequencies, the gamma
ray region of the electromagnetic spectrum merging into the
adjacent lower energy x-ray region. Gamma ray bursts are intense
flashes of gamma rays detected at energies up to 10^(6) electron
volts. They were discovered by US Air Force satellites in the
1960s 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. ... ... B.J. McNamara and T.E.
Harrison present a review of the history of gamma ray burst
research, the authors making the following points: 1) The origin
of gamma-ray bursts -- which are among the most energetic events
in the Universe -- has puzzled astronomers for 25 years. Since
1991, new events have been discovered at a rate of about one per
day, but because their positions were poorly determined, the
objects responsible for these outbursts could not be identified.
Now, following the launch of the *BeppoSAX satellite in 1996,
gamma-ray bursts have been rapidly and accurately located, which
has led to the breakthrough discoveries of x-ray and optical
counterparts in 1997, and the demonstration that these objects
are in general very distant. 2) The cosmological distances of
gamma-ray bursts implied by their measured *redshifts requires
that whatever process creates them releases a tremendous amount
of energy. Current models assume that gamma-ray bursts are
associated with compact objects that expel matter at highly
*relativistic velocities. As the expanding shell (often called a
"fireball") sweeps up material from the ambient environment, it
loses energy and radiates at longer wavelengths. 3) There are a
number of different gamma-ray burst fireball models, the
differences among the models consisting in the manner in which
the fireball is energized (impulsively or continuously), the
geometry of the fireball (spherical or beamed), the density of
the surrounding medium (constant or decreasing with radius), and
the manner in which the fireball dissipates its energy. More
observational data will be needed to differentiate among these
various possibilities.
-----------
B.J. McNamara and T.E. Harrison (New Mexico State University, US)
The optical counterparts of gamma-ray bursts.
(Nature 19 Nov 98 396:233)
QY: Bernard J. McNamara, New Mexico State Univ. 505-646-2035
-----------
Text Notes:
... ... *neutron stars: During the terminal stages of the
evolution of a star, part of the mass of the star is blown off
and lost. If the remnant mass is between 1.4 and 2 to 3 solar-
masses, the star will collapse into a neutron star, a body with a
radius of only 10 to 15 kilometers, but with a core so dense that
its component protons and electrons have merged into neutrons.
The average density of a neutron star is 10^(15) grams per cubic
centimeter, and the weight of an object on the surface of a
neutron star would be 10^(11) its weight on the surface of the
Earth. Neutron stars apparently have an outer shell of iron, but
it is iron like no Earth iron, an iron of 4 orders of magnitude
greater density. Theory predicts that a neutron star should
rotate very rapidly, be extremely hot, and have an intense
magnetic field.
... ... *BeppoSAX satellite: An Italian x-ray astronomy mission
launched in 1996 with participation from the Netherlands and the
European Space Agency. The satellite carries a range of broad-
band spectroscopic instruments.
... ... *redshifts: 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. The furthest galaxy on record is at a
redshift z = 4.92), which implies a distance of approximately 13
billion light years.
... ... *relativistic velocities: In general, a velocity
approaching that of light.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 25Dec98
-------------------
Related Background:
ANALYSIS OF A GAMMA RAY BURST FROM A HIGH REDSHIFT GALAXY
... Knowledge of the properties of gamma-ray bursts has
increased substantially following recent detections of
counterparts at x-ray, optical, and radio wavelengths. But the
nature of the underlying physical mechanism that powers these
sources remains unclear. An important question is the total
energy in the burst, for which an satisfactory estimate of the
distance is required, and until now the best estimate is that the
bursts lie at cosmological distances. ... ... Kulkarni et al (16
authors at 9 installations, US IN IT) now report identification
of the host galaxy of a previously optically detected burst
(GRB971214), with a determination of the galaxy redshift at z =
3.42. When combined with the measured flux of gamma-rays from the
burst, this large redshift implies an energy of 3 x 10^(53) ergs
in the gamma-rays alone, assuming the emission is isotropic. This
is much larger than the energies previously considered, and the
authors suggest it poses a challenge for theoretical models of
the bursts.
QY: S.R. Kulkarni (srk@surya.caltech.edu)
(Nature 7 May 98 393:35) (Science-Week 29 May 98)
-------------------
Related Background:
GAMMA RAY BURST FIREBALL MODEL MAY NEED REVISION
... 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. ... ... Castro-Tirado et al (27 authors at 15
installations, ES DE SE DK IT UK US) report an optical transient
from a gamma ray burst (GRB 970508) imaged 4 hours after the
event, displaying a strong ultraviolet excess and reaching
maximum brightness 2 days later. The optical spectra did not show
any emission lines, and no variations on time scales of minutes
were observed for 1 hour during the decline phase. The authors
suggest the observations are incompatible with the fireball and
afterglow models of gamma ray bursts, and that another physical
mechanism may be responsible for the constant phase seen the
first few hours after the burst occurs. QY: T. Broadhurst, Univ.
of Calif. Berkeley, Dept. Astronomy 510-643-8520
(Science 13 Feb 98) (Science-Week 27 Feb 98)
3. ON THE FOSSIL TRACKS OF VERTEBRATES
Ichnology is the study of fossil footprints, i.e., vertebrate
tracks, and apparently the field is in the midst of a
renaissance. One central focus in the field is to delineate the
relations between fossil footprints and actual bone structure,
since the bones of the vertebrate foot are often heavily padded
with tissue, particularly in large animals. ... ... Martin G.
Lockley reviews the field, the author making the following
points: 1) At a time when paleontology has been aided by
revolutions in molecular paleontology and *cladistics, the study
of *tetrapod tracks has also grown steadily and has undergone its
first true renaissance since the inception of the field more than
150 years ago. This renaissance has been largely due to an
increase in the discovery and documentation of new sites. 2) The
present empirically derived database in ichnology helps define
and measure spatial and temporal incompleteness in the skeletal
record of terrestrial vertebrates. It thus possible to focus on
which parts of the fossil record must be described
ichnologically, osteologically, or by both methods. 3) A holistic
view indicates that many questions about foot morphology,
posture, locomotion, behavior, terrestrial vertebrate
paleontology, stratigraphy, and information biases cannot be
fully understood without consideration of the data encoded in the
track record.
-----------
Martin G. Lockley (University of Colorado Denver, US)
The vertebrate track record.
(Nature 3 Dec 98 396:429)
QY: Martin G. Lockley, University of Colorado Denver 303-556-2398
-----------
Text Notes:
... ... *cladistics: A mode of classification based principally
on groupings (taxa) defined in terms of shared similar
characters. A "clade" is a cluster of taxa derived from a single
common ancestor. A "cladogram" is a tree diagram representing
phylogenetic relationships among taxa.
... ... *tetrapod: The literal meaning is "four-footed". In
general, the term refers to four-footed members of land-evolved
vertebrates, e.g., to four-footed amphibia, reptiles, and
mammals.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 25Dec98
4. CELL BIOLOGY: ON ASYMMETRIC CELL DIVISION
In biological cells that divide, cell division can occur after
DNA replication. Cell growth, which occurs throughout the cell
cycle, typically causes a cell to double in size by the time it
is ready to divide. Most cells then undergo "binary fission",
which partitions the cell down the middle and generates two
identical new cells. Certain types of cells, however, undergo an
asymmetric division process. In the context of this report, the
term "asymmetric cell division" refers to cell division producing
two daughter cells that exhibit distinct fates. In all organisms
in which development has been studied extensively, ranging from
bacteria to mammals, asymmetric cell division is one of the
apparent origins of cell diversity. The central question in this
field is what are the molecular mechanisms responsible for the
programmed asymmetry? ... ... N. Hawkins and G. Garriga present a
review of current research on asymmetric cell division, the
authors making the following points: 1) Asymmetric cell division
can be achieved by either intrinsic or extrinsic mechanisms.
Intrinsic mechanisms involve the preferential segregation of cell
fate determinants to one of two daughter cells during *mitosis.
Asymmetrically segregated factors that bind cell fate
determinants and orient the *mitotic spindle may also be
necessary to ensure the faithful segregation of determinants into
only one daughter cell. 2) Extrinsic mechanisms involve cell-cell
communication. In *metazoans, the social context of a dividing
cell provides positional information and opportunity for
cell-cell interactions. Interactions between daughter cells or
between a daughter cell and other nearby cells can specify
daughter cell fate. Interaction between a progenitor cell and its
environment can influence *cell polarity by directing spindle
orientation and an asymmetric distribution of developmental
potential to daughter cells. 3) Recent studies have indicated
that a combination of intrinsic and extrinsic mechanisms specify
distinct daughter cell fates during asymmetric cell division. In
the past few years, rapid progress has been made in elucidating
the mechanisms underlying asymmetric cell division, but several
outstanding questions remain to be addressed, in particular the
mechanism of the establishment of *neuroblast polarity.
-----------
N. Hawkins and G. Garriga (University of California Berkeley, US)
Asymmetric cell division: From A to Z.
(Genes & Development 1 Dec 98 12:3625)
QY: Nancy Hawkins, Univ. of Calif. Berkeley 510-642-6000.
-----------
Text Notes:
... ... *mitosis: (karyokinesis) Division of the cell nucleus in
eukaryotic cells (i.e., cells with internal membrane-bound
organelles).
... ... *mitotic spindle: A structure composed of *microtubules
that separates the two sets of chromosomes during cell division
in eukaryotes.
... ... *microtubules: Microtubules are part of the cytoskeleton
of biological cells, the quasi-rigid matrix that among other
things determines cell shape. The microtubules are 25 nanometers
in diameter, and composed of the protein tubulin. They occur in
regular arrays in cilia, flagella, the mitotic spindle, and in
the cytoplasm in general, and they contribute not only to cell
shape, but also to cell motility.
... ... *metazoans: In general, the term "metazoa" refers to all
multicellular animals. Among important distinguishing
characteristics of metazoa are cell differentiation and
intercellular communication. For certain multicellular colonial
entities such as sponges, some biologists prefer the term
"parazoa".
... ... *cell polarity: In general, non-random organization of
the interior of the cell.
... ... *neuroblast polarity: Neuroblasts are embryonic cells
destined to be differentiated into the cells of nerve tissue.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 25Dec98
-------------------
Related Background:
ON ASYMMETRIC CELL DIVISION
Asymmetric cell division, in which a cell divides into two cells
of different developmental potentials, is a fundamental means of
generating cell diversity. In principle, asymmetric cell divis-
ions may involve extrinsic or intrinsic factors. With extrinsic
factors, daughter cells are initially equivalent but adopt
different fates as the result of the interactions of the daughter
cells with each other or with their environment. With intrinsic
factors, unequal amounts of cell-fate determinants are partit-
ioned into the two daughter cells. The mechanisms underlying
asymmetric cell division have been studied in organisms ranging
from bacteria, yeast, worms, and flies, to mammals. Intrinsic
determinants have been identified in several systems, and at
present the key molecular questions are 1) What controls the
asymmetric localization of the determinants during mitosis? and,
2) How do the determinants control daughter cell fate?
... ... Jan and Jan (University of California San Francisco, US)
review this field, focusing primarily on the Drosophila nervous
system, using other systems for comparison. The authors propose
that with the recent identification of intrinsic cell-fate
determinants for asymmetric cell division in several systems,
biologists have begun to gain insight into the cellular mechan-
isms by which these determinants are preferentially segregated
into one of the two daughter cells during mitosis. The authors
suggest that the intensive efforts directed at several
experimental systems will soon identify common and varied
mechanisms involved in asymmetric cell divisions.
QY: Yuh Nung Jan, Dept. of Physiol., Univ. of Calif. San
Francisco 415-476-4044.
(Nature 23 Apr 98 392:775) (Science-Week 15 May 98)
5. ON THE FOLDING OF SECRETORY AND MEMBRANE PROTEINS
The mechanisms responsible for the assumption of specific
configurations by specific proteins are of considerable
importance for any understanding of molecular dynamics in living
cells, and in recent years these folding mechanisms have also
become a focus of medical interest. Genetic errors may result in
abnormal synthesis of proteins, abnormal folding and processing
of proteins after they are synthesized, or changes in the
functional properties of proteins. Although the synthesis of
proteins begins in the cytoplasm, many proteins are destined to
be expressed on the cell surface (e.g., *surface-recognition
molecules, *ion channels, *receptors, *adhesion molecules) or
secreted (e.g., hormones, *growth factors, *extracellular matrix
proteins, *proteolytic enzymes). Newly synthesized membrane and
secretory proteins are transported into the *endoplasmic
reticulum, the internal membranous network of the cell, in a
largely unfolded state, and when they leave the endoplasmic
reticulum to be either secreted or become part of the cell
membrane, the proteins are apparently almost completely folded
and most protein multi-subunit complexes are fully assembled. The
key folding mechanisms, therefore, occur in the endoplasmic
reticulum. ... ... G. Kuznetsov and S.K. Nigam present a detailed
review of current ideas concerning the medical ramifications of
the folding of secretory and membrane proteins, the authors
making the following points: 1) The folding of membrane and
secretory proteins is a complex process that occurs in the
endoplasmic reticulum. The process involves a number of discrete
reactions facilitated by specific folding enzymes and a group of
endoplasmic reticulum-specific molecular *chaperone proteins. 2)
Perturbations in protein folding and assembly are emerging as an
important mechanism of disease. Although there is considerable
evidence that misfolding of mutated proteins and their retention
in the endoplasmic reticulum are key steps in the molecular
pathogenesis of a variety of genetic diseases, little is known
about how protein folding in the endoplasmic reticulum is
affected by many acute illnesses. 3) A deeper understanding of
the mechanisms of protein folding in the endoplasmic reticulum is
likely to lead to novel therapeutic approaches designed to
minimize cell injury and enhance recovery. The authors tabulate
13 human genetic disorders in which protein misfolding has an
apparent major role. The review contains 69 references.
-----------
G. Kuznetsov and S.K. Nigam (Harvard Medical School, US)
Folding of secretory and membrane proteins.
(New England J. Med. 3 Dec 98 339:1688)
QY: Sanjay K. Nigam, Harvard Univ. Medical School 617-432-1550.
-----------
Text Notes:
... ... *surface-recognition molecules: In general, this term
refers to molecules that are attached to the surfaces of cells
and which are involved in the recognition of cells by each other.
... ... *ion channels: Ion channels are protein channels in cell
membranes that allow ions to pass from extracellular solution to
intracellular solution and vice versa. Most ion channels are
selective, allowing only certain ions to pass, and an individual
cell has ion channels with various ion selectivities. The
selectivity of an ion channel can be "gated", the channel
effectively opened or closed, and ion channels are said to
*voltage-gated or *ligand- gated, depending on how the change in
selectivity is provoked.
... ... *receptors: In this context, the term refers to molecules
or parts of molecules with affinities for specific ligands.
... ... *adhesion molecules: Molecules expressed on the surface
of a cell that mediate the adhesion of the cell to other cells or
to the extracellular matrix. Adhesion molecules bind to receptors
that are classed collectively as "integrins". Abnormalities in
cellular adhesion properties are characteristic of many types of
cancer cells.
... ... *growth factors: A group of small secreted polypeptides
that bind to receptors on certain specific target cells and
stimulate cell division in those target cells.
... ... *extracellular matrix proteins: In this context, the
complex network of macromolecules lying between cells where the
cells form tissues.
... ... *proteolytic: A general term for the breakdown of
proteins via the hydrolysis of peptide bonds.
... ... *endoplasmic reticulum: A complex system of flattened
sacs in eukaryotic cells, the site of many important syntheses,
apparently including the production of new surface membrane.
... ... *chaperone proteins: These are proteins required for the
proper folding and/or assembly of another protein or protein
complex.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 25Dec98
-------------------
Related Background:
PROTEIN-FOLDING MECHANISMS IN PROKARYOTES VS. EUKARYOTES
In biological systems, proteins are the molecules that do most of
the biological work, and the various proteins are the ultimate
expression of the genome of any organism. As polymers, proteins
are similar to the polymers known to polymer chemists, but the
chemical activities of proteins (and their biological functions)
depend mostly on higher-order folding into specific configur-
ations rather than on quasi-crystalline backbone arrays, as is
often the case in non-biological polymer chemistry. It is these
specific configurations that are responsible for the important
specificity and high catalytic power of the proteins that are
enzymes. The configurations, in turn, are an ultimate result of
amino acid sequences which form the backbone of proteins,
sequences which are not simple, as are the backbone sequences of
most non-biological polymers, but are specific, cryptic (coded),
and heterogenous. It is now recognized that complex proteins
usually have more than one folding domain, each involving a
sequence of 100 to 300 amino acids. The entire folding
architecture of a complex protein must be precisely constructed
in order for protein functionality to exist. Which provokes the
question of how the specific folding of particular proteins is
ensured by the biological system. The answer is evident for
simple proteins in vitro: the final configuration is
predetermined by the amino acid sequence, there being a single
energetically favored configuration that will always be attained
at equilibrium. This is Anfinsen's Rule, first proposed by the
protein biochemist C. B. Anfinsen more than 30 years ago. In
vivo, however, and particularly for complicated proteins, the
situation is more involved. This week W. J. Netzer and F. U.
Hartl (Sloan Kettering Cancer Center, NY US; Max Planck Inst.
Biochemistry, Martinsried DE) report an analysis of the
differences between protein folding in prokaryotes (organisms,
such as bacteria, without membrane-bound organelles such as the
nucleus) and eukaryotes (organisms with membrane-bound
organelles). Perhaps the most interesting difference is that in
prokaryotes protein folding is delayed until translation (final
synthesis by the ribosome) is completed (post-translational
folding), while in eukaryotes folding of each protein domain
occurs as each domain is translated (co-translational folding).
One result is that new prokaryote proteins can often be
misfolded. There are helper proteins at work in both prokaryotes
and eukaryotes to chaperon the proteins to their final
configurations, but there is still more possibility for errors in
the prokaryotes. One important consequence of this analysis is
that when bacteria are genetically engineered to synthesize human
protein for clinical use, the susceptibility of prokaryote
protein synthesis to folding errors must be considered.
(Nature 24 Jul 97) (Science-Week 8 Aug 97)
6. EVIDENCE FOR A FACTORY MODEL OF DNA REPLICATION
For all organisms, the production of viable progeny depends on
the faithful replication of DNA by the enzyme DNA polymerase,
which incorporates nucleoside triphosphates into a DNA chain.
This enzyme is actually a multi-enzyme complex that takes
different forms in *prokaryotes and *eukaryotes. Two general
models have been proposed for DNA replication. In one model, DNA
polymerase moves along the template DNA (like a train on a
track); in the other model, the polymerase is stationary (like a
factory), and the template DNA is pulled through.
... ... K.P. Lemon and A.D. Grossman present the results of a
study to distinguish between the two models. The authors report
they visualized DNA polymerase of the bacterium *Bacillus
subtilis in living cells by the creation of a *fusion protein
containing the DNA polymerase catalytic subunit (PolC) and green
fluorescent protein (GFP). The authors report the PolC-GFP entity
was found localized at discrete intracellular positions,
predominantly at or near mid-cell, rather than being distributed
randomly. The authors propose their results suggest that the
polymerase is anchored in place, thus supporting the model in
which the DNA template moves through polymerase.
-----------
K.P. Lemon and A.D. Grossman (Mass. Inst. of Technol., US)
Localization of bacterial DNA polymerase: Evidence for a factory
model of replication.
(Science 20 Nov 98 282:1516)
QY: Alan D. Grossman
-----------
Text Notes:
... ... *prokaryotes: In general, cells without a cell nucleus
and other membrane-bound organelles.
... ... *eukaryotes: In general, cells with a cell nucleus and
other membrane-bound organelles.
... ... *Bacillus subtilis: The genus Bacillus is a group of
free-living rod-shaped bacteria, some species of which produce
antibiotics. The genome of B. subtilis has been completely
sequenced.
... ... *fusion protein: In this context, a "fusion protein" is a
protein that results from the fusion of two genes. The essential
idea here is the fusion of the gene for DNA polymerase with the
gene for the green fluorescent protein, so that when and where
the new DNA polymerase-fluorescent protein is expressed it can be
located by its fluorescent moiety. (See below for a related use
of the technique.)
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 25Dec98
-------------------
Related Background:
NEW FUSION PROTEIN ENABLES VISUALIZATION OF DNA IN LIVE CELLS
Eukaryotic cells are cells having membrane bound organelles such
as a nucleus, and the term "histones" refers to a group of 8
small basic (as opposed to acidic) proteins found in combination
with nucleic acids in eukaryotic chromosomes. The histone-nucleic
acid complexes are essential aspects of chromosome molecular
architecture. ... ... A class of DNA-histone assemblies typical
of many cancer cells called "double minute chromosomes" have
until now been difficult to visualize because of their small
size. Now a group at the Salk Institute (US) has developed a
working method involving a fluorescent fusion protein. The method
involves fusing a human histone gene to the gene for a green
fluorescent jellyfish protein, with the combined new gene
expressed in a human cell line.
QY: T. Kanda, Salk Institute, 10010 N. Torrey Pines Road, La
Jolla, CA 92037 US.
(Curr. Biol. 8:377 1998) (Science-Week 27 Mar 98)
7. REOVIRUS DESTRUCTION OF TUMORS
An oncogene is the activated form of a proto-oncogene. A proto-
oncogene is a normal cellular gene that upon specific alteration
(activation), acts to induce a cancerous state. Transformation
from proto-oncogene to oncogene may involve a virus, a mutation,
chromosomal translocation, etc. Reoviruses are a genus within the
*Reoviridae family of medium-sized viruses (60 to 80 nanometers
in diameter), the viruses in this family having a double-stranded
RNA genome. The family includes human rotaviruses, the most
important cause of infant gastroenteritis around the world.
Reoviruses (again, a genus [subset] of the family Reoviridae)
are not known to be an important cause of any serious human
disease, although there is a human reovirus that infects the
upper respiratory and gastrointestinal tracts with mild or no
symptoms. Active mutations of a proto-oncogene called "Ras" have
been found in approximately 30 percent of all human tumors,
primarily in pancreatic tumors (90 percent), *sporadic colorectal
tumors (50 percent), lung *carcinomas (40 percent), and *myeloid
leukemia (30 percent). Human reovirus is known to require an
active *Ras signaling pathway for infection of cultured cells.
... ... M.C. Coffey et al now present the results of a study to
investigate whether the requirement of human reovirus for an
active Ras pathway can be exploited for cancer therapy. Immune-
deficient mice bearing tumors were treated with the virus. The
authors report that a single intratumoral injection of virus
resulted in regression of tumors in 65 to 80 percent of the mice.
Treatment of immune-competent mice bearing tumors also resulted
in tumor regression, although a series of injections were
required. The authors suggest that with further work reovirus may
have applicability in the treatment of cancer.
-----------
M.C. Coffey et al (University of Calgary, CA)
Reovirus therapy of tumors with activated Ras pathway.
(Science 13 Nov 98 282:1332)
QY: Patrick W.K. Lee
-----------
Text Notes:
... ... *Reoviridae: The nomenclature here is confusing. The
family Reoviridae contains 6 genera (subsets): reovirus,
orbivirus, rotavirus, cypovirus, phytoreovirus, fijivirus. The
last two are plant viruses. The prefix "reo-" derives from
(r)espiratory (e)nteric (o)rphan.
... ... *sporadic: In this context, the term "sporadic" means
non-familial.
... ... *carcinomas: In general, a carcinoma is any malignancy
derived from epithelial tissue. In animals, epithelial cells
compose the cell layers that form the interface between a tissue
and the external environment, for example, the cells of the skin,
the lining of the intestinal tract, and the lung airway
passages.
... ... *myeloid leukemia: (granulocytic leukemia) In general, a
form of leukemia characterized by proliferation of bone marrow
cells or cells derived from bone marrow cells.
... ... *Ras signaling pathway: is an oncogene of which
there are at least 3 varieties. The Ras proteins play a pivotal
role in regulating growth and differentiation in nearly every
eukaryotic cell studied. The 2 Ras subfamilies of proteins, Rho
and Rac, are involved in relaying signals from cell-surface
receptors to the *actin cytoskeleton.
... ... *actin cytoskeleton: Actin is a family of ubiquitous
structural proteins present in all eukaryote cells, and the term
"cytoskeleton" refers to the quasi-rigid matrix that among other
things determines cell shape.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 25Dec98
-------------------
Related Background:
NEW TECHNIQUE USES COMMON COLD VIRUS TO KILL TUMOR CELLS
Human cells have a suicide program that is triggered by a
protein (p53) when the cell's genetic machinery is damaged. Some
viruses possess a gene that inactivates the protein p53, which
enables them to use the cell's genetic apparatus to reproduce,
with the eventual death of the host cell. The common cold virus
(adenovirus) is one of these viruses. That is fact #1. Fact #2
is that in many kinds of tumor cells, their protein p53 has
become intrinsically inactivated. Fact #3 is that a strain of
adenovirus exists that has lost the p53 jamming gene. This
mutant adenovirus will therefore be lethal to tumor cells with
already inactivated p53, but not to ordinary cells. So Frank
McCormack and his colleagues (Onyx Pharmaceuticals, Richmond CA
US) injected the mutant strain of adenovirus into head and neck
tumors in patients who had failed to respond to surgery,
radiation, or chemotherapy, and they found significant
destruction of tumors in 25% of the patients. The mutant
adenovirus killed the tumor cells in these large, refractory
cancers. These are preliminary trials, but the beginning of
what may be an extremely important approach to cancer therapy --
the use of pathogens with a specificity for tumor cells. The
results were reported at the recent meeting of the American
Society of Clinical Oncology.
(New York Times 20 May) (Science-Week 22 May 97)
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
LETTER: ON THE ORIGIN OF THE SOLAR SYSTEM
Professor John A. Wood (SCIENCE-WEEK 11 Dec 98; see related
background below) claims that the "amazing diversity" in the
Solar System today is consistent with Kant's hypothesis of a
nebular origin. Indeed, cooling an interstellar cloud of gas and
dust may produce chemical diversity, but not closely linked
isotopic irregularities (#1). Different isotopes of an element
develop at different times and different depths in stars (#2).
Isotopic irregularities thus become coupled with chemical layers
of stars at the source. Once stellar debris becomes mixed within
an interstellar cloud, cooling and condensation cannot reproduce
this initial coupling of chemical and isotopic heterogeneities. A
good example of these isotopic variations is xenon, with nine
stable isotopes. In bulk *chondritic meteorites, abundances of
xenon isotopes are unlike those on Earth (#3), but xenon isotopes
in iron-sulfide (troilite) of meteorites are like those on Earth
(#4). Earth-like xenon also occurs in Mars, the other planet rich
in iron-sulfide (#5). Another isotopic pattern is the "strange"
xenon trapped with abundant helium in diamonds from chondritic
meteorites (#6,7). The planet Jupiter contains large amounts of
helium and the main constituent of diamonds, carbon. The Galileo
space probe revealed "strange" xenon in Jupiter as well (#8,9).
Yet a fourth isotopic configuration is seen in the *solar wind,
where the lighter isotopes of xenon and other elements are
systematically enriched. It is believed that diffusion inside the
Sun selectively moves lighter elements like hydrogen and helium
to the solar surface (#10). Diffusion of Earth-like xenon mimics
that in the solar wind, as expected if the Sun's surface
camouflages an interior rich in iron and sulfur (#11). Such
widespread isotopic diversity implies another origin than cooling
and condensation. Modern textbooks on astronomy and geochemistry
show remarkably similar chemical gradients in our planetary
system, in the Earth, and in highly evolved, massive stars: Iron
is enriched in the center of each; light elements like hydrogen,
helium and carbon are abundant in the outer regions; and
intermediate-weight elements like oxygen and silicon are enhanced
in the middle part. These chemical gradients and the closely
coupled isotopic diversity seen today could very possibly be
remnants of a supernova that produced the Solar System (#12). It
is my personal conviction that the "amazing diversity" of our
Solar System came from a supernova that produced our elements and
gave birth to the Solar System in a catastrophic explosion five
billion years ago (#13). Ironically, *Comte de Buffon postulated
such a cataclysm for the origin of the Solar System in 1745, a
decade before Immanuel Kant's nebular hypothesis. More complete
details are available from the author.
-----------
Oliver K. Manuel
Professor
University of Missouri
Department of Chemistry
-----------
Reference Notes:
... #1: J.T. Lee et al (Comment Astrophys. 18: 335 1997)
... #2: E.M. Burbidge. et al (Rev. Mod. Phys. 29:547 1957)
... #3: J.H. Reynolds (Phys. Rev. Lett. 4: 351 1960)
... #4: J.T. Lee et al (Geochem. J. 30: 17 1996)
... #5: J.A. Wood (Proc. of the Robert Welch Conf. on
Cosmochemistry, W.A. Milligan, ed., fig. 10, p. 339 1978)
... #6: O.K. Manuel and D.D. Sabu (Science 195: 208 1977)
... #7: D.D. Sabu and O.K. Manuel (Meteoritics 15:117 1980)
... #8: O.K. Manuel et al (Bull. AAS 30:852 abstract 29.01 1998)
... #9: O.K. Manuel et al (J. Radioanal. Nucl. Chem. v. 238, in
press 1998)
... #10: O.K. Manuel and G. Hwaung (Meteoritics 18:209 1983)
... #11: O.K. Manuel (Meteoritics & Planetary Science 33: A97
1998)
... #12: L.L. Oliver et al (J. Inorg. Nucl. Chem. 43:2207 1981
Fig.6)
... #13: P.K. Kuroda and W.A. Myers (Radiochim. Acta 77:15 1997)
-----------
Text Notes:
... ... *chondritic meteorites: (chondrites) A type of stony
meteorite. Most but not all chondrites consist of an
agglomeration of millimeter-sized globules (chondrules) that are
thought to be unchanged since the original condensation out of
the nebula from which the sun and solar system formed.
... ... *solar wind: The solar wind is the steady flow of charged
particles, consisting primarily of protons and electrons, from
the solar corona into interplanetary space. The solar wind
particles have energies high enough so they can escape the sun's
gravitational field, but the wind is influenced by the sun's
magnetic field, and the particles can be trapped by planetary
magnetic fields.
... ... *Comte de Buffon (1707-1788): (Georges Buffon) A French
naturalist, but also a member of the Royal Society of England. In
1745 Buffon suggested that the Earth might have been created by
the catastrophic collision of a massive body with the Sun 75,000
years ago. This was perhaps the first attempt in Christian Europe
to consider the Earth as older than the 6000 year limit
apparently set by the biblical Book of Genesis.
-------------------
Text Notes by SCIENCE-WEEK http://scienceweek.com 25Dec98
-------------------
Related Background:
ON THE ORIGIN OF THE SOLAR SYSTEM
During the past two centuries, astronomers have considered two
types of theories for the origin of our Solar System planets.
Catastrophic theories proposed that these planets formed from
some improbable cataclysm such as the collision of the sun and
another star, while gradualist theories proposed that the planets
formed naturally with the Sun. At the present time, as a result
of evidence accumulated during the past five decades, the
gradualist idea is the consensus idea, and nearly all astronomers
now believe that planets form naturally as a by-product of star
formation. ... ... John A. Wood presents an extensive review of
current ideas concerning the origin of the Solar System, and the
author makes the following points: 1) The current theory is that
the Sun and the planets were born from a rotating disk of cosmic
gas and dust (the "solar nebula"), and the flattened form of the
disk constrained the planets that formed from it to have orbits
lying in the same plane, or nearly so, the planets all moving in
the same direction in which the disk had turned. 2) The idea of a
solar nebula was first formulated in 1755 by *Immanuel Kant.
Although his treatment of the problem was only qualitative, its
precepts were remarkably similar to those considered fundamental
today, and at the present time, Kant's original idea is
considered to be correct: stars and their disks form in much the
same way he pictured, the formation resulting from the
gravitational collapse of huge volumes of thinly dispersed
interstellar gas and dust onto appropriate nuclei. 3) The present
view is that the solar nebula was hot near its center, tapering
off to a cold region, then a very cold region at its outermost
margins. Thus, the falloff of nebula temperature with
heliocentric distance defined 3 radial zones. The innermost zone
was too warm for water to condense as ice; objects forming in the
innermost zone consisted entirely of *silicate minerals and other
*refractory materials, and ultimately became the terrestrial
planets (Mercury, Venus, Earth, and Mars). The next zone of the
solar nebula was colder, water ice was stable, and a vast
blizzard of snowflakes gave rise to the much larger Jovian
planets (Jupiter, Saturn, Uranus, and Neptune). In the outermost
and thus coldest zone of the solar nebula, condensed matter was
also icy, but matter was too sparsely distributed to accrete into
sizable planets; instead matter remained dispersed in small icy
planetesimals -- comet nuclei -- in what is now called the
*Kuiper belt. Evidence suggests the planets assembled themselves
quickly: Although the process differed in detail from zone to
zone, virtually everything was in place within 10 million years,
by which time the solar nebula had largely dissipated. 4) Nearly
four centuries of telescopic observation, combined with four
decades of space exploration, have taught us this essential truth
about the Solar System: While the Sun and its planetary system
surely arose from one grand spiral of gas and dust in a flurry of
collective activity, the results are hardly a homogeneous set of
characterless orbiting entities. Instead this grand scheme of
formation has yielded amazing diversity in the properties of the
various objects in the Solar System.
-----------
John A. Wood (Smithsonian Astrophysical Observatory, US)
Forging the planets.
(Sky and Telescope January 99)
QY: John A. Wood, Smithsonian Astrophysical Observatory,
Cambridge, MA US.
-----------
Text Notes:
... ... *Immanuel Kant (1724-1804): Kant is best known as a
philosopher, but he first studied mathematics and physics, and
the year he obtained his doctorate degree (1755) he published his
physical view of the Universe in *General History of Nature and
Theory of the Heavens). In this treatise, Kant described the
solar nebula hypothesis of planet formation, suggested that our
own galaxy is a lens-shaped collection of stars and that other
such "island universes" exist, and suggested that *tidal friction
slows the rotation of the Earth. All three propositions are the
current view in astrophysics.
... ... *tidal friction: A force between the oceans of the Earth
and the ocean floors caused by the gravitational attraction of
the Moon.
... ... *silicate minerals: (silicates) The most important and
abundant group of rock-forming minerals.
... ... *refractory materials: (refractory minerals) Minerals
resistant to decomposition by heat, pressure, or chemical attack.
The term is most commonly applied to heat resistance.
... ... *Kuiper belt: In 1951 the astronomer Gerard P. Kuiper
(1905-1973) postulated the existence of a belt of objects beyond
the orbit of Pluto. Both the existence and nature of the objects
were matters of speculation for decades, and finally in 1992
Jewitt and Luu identified the first Kuiper object. The current
estimate is that as many as 10^(8) objects larger than 10
kilometers in diameter may exist in what is called the "Kuiper
belt", a disc that hugs the plane of the planetary system and
lies between 35 and 1000 *AU from the Sun. Observations to date
have yielded some 55 trans-Neptune bodies with radii on the order
of 100 km or larger, and Pluto is considered by some astronomers
to be a member of this population.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 11Dec98
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