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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.
October 9, 1998 -- Vol. 2 Number 41
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I can live with doubt and uncertainty and not knowing. I think
it's much more interesting to live not knowing than to have
answers which might be wrong. I have approximate answers and
possible beliefs and different degrees of certainty about
different things, but I'm not absolutely sure of anything and
there are many things I don't know anything about...
-- Richard Feynman (1918-1988)
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Contents of This Issue:
1. Decline in Minority Graduate Admissions
2. A Mysterious Dust Clump in a Binary Star System Disk
3. On the Blockade of the Cosmic Map by Our Own Galaxy
4. Evidence Suggesting Fe(III) Reduction by Early Earth Bacteria
5. Antibodies Specific for Fullerenes
6. On Peptide Nucleic Acids
7. RNA-Catalyzed Nucleotide Synthesis
8. Localization of Sound by Early-Blind Human Subjects
9. Biological Action of Leptin as an Angiogenic Factor
10. Angiogenesis: Inhibition by Neomycin
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1. DECLINE IN MINORITY GRADUATE ADMISSIONS
In 1996, voters in California approved an anti-affirmative action
referendum, and that same year a federal district court banned
affirmative action at universities in Texas, Louisiana, and
Mississippi. Educators and federal executive branch officials
feared the consequence of the referendum and court decision would
be a drop in minority university enrollments nationwide, and the
data now coming in apparently justifies their fears. A report
released the week of September 11th by the American Association
for the Advancement of Science presents the results of analysis
of admissions data for the past 4 years from science and
engineering graduate programs at 93 major research universities.
From 1994 to 1996, there was little change in black graduate
admissions and a slight increase in Hispanic admissions
(approximately 5 percent). But in 1997, black admissions declined
20 percent and Hispanic admissions declined 18 percent from the
previous year. The declines are attributed to the uncertainty of
university administrators: "They don't know what is allowed and
what is not."
-----------
M. Barinaga (~Science~): Graduate Admissions Down for Minorities.
(Science 18 Sep 98 281:1778)
QY: Marcia Barinaga
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Summary by SCIENCE-WEEK http://scienceweek.com 9Oct98
-------------------
Related Background:
MINORITY FACULTY AND ACADEMIC RANK IN MEDICINE
Recent efforts to improve the representation of minority faculty
in US academic medicine have focused on increasing the number of
minority physicians who pursue academic careers. However, the
number of minority students entering US medical schools has
plateaued, despite efforts to achieve racial and ethnic diversity
in these schools. At the present time, only 3.9 percent of all US
medical faculty identify themselves as black, Native American,
Mexican American, or Puerto Rican, and these groups have been
classified as underrepresented in medicine compared to their
representation in the general population. Asian Americans are
currently not classified as underrepresented. ... ... A. Palepu
et al now report a study to determine whether minority faculty
were as likely as majority faculty to have attained senior rank
(associate professor or full professor) after adjusting for other
factors that typically influence promotion. The study consisted
of a self-administered mailed survey of US medical school faculty
using the Association of American Medical Colleges database, the
sample stratified by department, graduation cohort, and sex. Of
1807 respondents, 54 percent had attained senior academic rank.
The authors report that after adjusting for the medical school,
department, years as medical school faculty, number of peer-
reviewed publications, receipt of research grant funding,
proportion of time in clinical activities, sex, and tenure
status, the odds ratios relative to white faculty of holding
senior rank were 0.33 for black faculty, 0.36 for Hispanic
faculty, and 0.58 for Asian faculty. The authors conclude that
minority faculty are less likely than white faculty to hold
senior academic rank, and they suggest this finding is not
explained by potential confounders such as years as a faculty
member or measures of academic productivity. The authors further
suggest that "medical school deans and department heads need to
foster and provided greater support for the careers of minority
faculty to ensure their equitable representation at all levels in
academic medicine."
-----------
A. Palepu et al (6 authors at 2 installations, US): Minority
faculty and academic rank in medicine.
(J. Amer. Med. Assoc. 2 Sep 98 280:767)
QY: Anita Palepu
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Summary by SCIENCE-WEEK http://scienceweek.com 25Sep98
2. A MYSTERIOUS DUST CLUMP IN A BINARY STAR SYSTEM DISK
The current nebula theory of planet formation proposes that
star-planet systems begin as a contracting cloud of gas and dust
that flattens into a rotating disk. The center of this cloud
becomes the star, and the planets eventually form in the disk of
the nebula. In the inner part of the nebula, the hottest part,
only high density minerals can form solid grains. The outer
regions are cooler, and in those regions icy materials of lower
density are formed. Planets grow from these solid materials,
beginning as dust grains, which grow by condensation and
accretion into planetesimals that range from a few centimeters to
a few kilometers in diameter. These planetesimals settle into a
thin plane around the star and accumulate into larger bodies, the
largest of which grow the fastest and eventually become
protoplanets. Once the star becomes a luminous object, the
remaining nebula is cleared as the star's radiation and the
stellar-wind (powerful streams of charged particles from the
star's surface) push the remnants out of the system. Thus ends
the phase of planet-building. As might be expected, the above
theory is also the current view of the history of our own solar
system. Since the details of disk formation, and the physical
properties of protoplanetary disks, can be modelled by
quantitative theory, the general idea is to investigate such
disks that are apparent around stars to test the theoretical
models. There is no way to do that with our own solar system,
because the protoplanetary disk is long gone. One needs young
stars, or such was the thinking until recently. The discovery in
1992 of apparent planets in orbit around a *pulsar has suggested
that planets may form around *post-Main Sequence stars and not
just around young stars. Gravitationally bound orbiting dust
disks are now known to be present around evolved stars other than
pulsars, an example being HD44179, an evolved star (probably
evolving into a *white dwarf) that is part of the binary system
that has expelled the gas and dust that constitute what is called
the Red Rectangle nebula. ... ... M. Jura and J. Turner now
report *high-angular-resolution observations at *millimeter and
submillimeter wavelengths of the dust disk associated with the
Red Rectangle. The authors report evidence for a dust clump with
an estimated mass near that of Jupiter in the outer regions of
the disk. The clump is larger than our Solar System, and is far
beyond where planet formation would normally be expected, which
leads the authors to suggest the nature and fate of the apparent
clump are a mystery.
-----------
M. Jura and J. Turner (University of California Los Angeles, US):
A mysterious dust clump in a disk around an evolved binary star
system.
(Nature 10 Sep 98 395:144)
QY: M. Jura
-----------
Text Notes:
... ... *pulsar: A pulsar is a pulsing source of stellar
radiation believed to originate with a *neutron star. They were
originally discovered at radio wavelengths, but there are
optical, gamma-ray, and x-ray pulsars, and some of the gamma-ray
pulsars are extremely powerful gamma-ray emitters.
... ... *neutron star: If at the terminal stages of a star's
evolution the remnant mass of the star is between 1.4 and 2 to 3
solar masses, the star will collapse into a neutron star, a body
with a radius of 10 to 15 kilometers, with a core so dense that
its component protons and electrons have merged into neutrons.
The average density of a neutron star is 10^(15) grams per cubic
centimeter, and the weight of an object on the surface of a
neutron star would be 10^(11) its weight on the surface of the
Earth. Neutron stars apparently have an outer shell of iron, but
it is iron like no Earth iron, an iron of 4 orders of magnitude
greater density. Theory predicts that a neutron star should
rotate very rapidly, be extremely hot, and have an intense
magnetic field.
... ... *post-Main Sequence stars: The Hertzsprung-Russell
diagram is a plot of stellar absolute magnitude against spectral
type, and is perhaps the most useful diagrammatic aid in
astrophysics. The Main Sequence is a region on the Hertzsprung-
Russell diagram where most stars lie, including our own sun. The
evolution of a star can be diagrammed as a movement along the
Main Sequence and an eventual branching off the Main Sequence to
regions associated with various types of old stars. The phrase
"post-Main Sequence stars" thus refers to old stars, i.e., stars
whose position on the H-P diagram is off the Main Sequence.
... ... *white dwarf: 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.
... ... *high-angular-resolution: In general, "resolution" is a
measure of the ability of an instrument to distinguish fine
detail, and the spatial or angular resolution of a viewing
instrument is the smallest angle between two point objects that
produces distinct images. The angular resolution depends on both
the wavelength at which the observations are made and on the
effective diameter or aperture of the viewing instrument.
... ... *millimeter and submillimeter wavelengths: The
submillimeter band lies between the microwave band (above 1
millimeter) and the far-infrared band (at about 0.1 millimeter).
Submillimeter wavelengths trace directly the emission from
dust that has been warmed by massive star-formation activity.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 9Oct98
-------------------
Related Background:
DUST DISKS AND EXTRASOLAR PLANETS
Paul Kalas (Max-Planck Institute for Astronomy Heidelberg, DE)
reviews current investigations concerning dust disks around stars
and the implications of the data for the existence of planets
around these stars. The author makes the following points: 1) One
of the important discoveries of the 1980s was the existence of
circumstellar disks of dust around some stars, the disks
apparently replenished by unseen parent bodies such as comets and
asteroids. 2) Some of these disks have recently been spatially
resolved by a new generation of ground-based instruments. An
example is the disk surrounding the star HR 4796, discovered in
1991 to have thermal emission from warm circumstellar dust. Two
observing teams have now mapped the emission from this dust disk
and revealed a peanut-shaped disk with the waist of the disk due
to an apparent central cavity (papers by Jayawardhana et al and
Koerner et al, in press). The data are interpreted by the authors
as indicating the existing of planets in formation around the
star, and so announced in news headlines (press releases by US
Harvard-Smithsonian Center for Astrophysics, US Jet Propulsion
Laboratory). Kalas, however, says the interpretation is premature
and not warranted by the data. 3) At about the same time as the
previous reports, maps of dust around the stars Vega, Fomalhaut,
and Beta Pictoris were published (Holland et al, *Nature*,
392:788 1988), and these maps were also interpreted as indicating
the presence of planets, but with differing bases for the
interpretations. Of the four stars, the data from HR 4796 and
Fomalhaut are interpreted as indicating planets creating central
cavities in dust formation, whereas the data from Vega and Beta
Pictoris are interpreted as indicating planets producing local
concentrations in their dust disks. The two interpretations are
apparently inconsistent. 4) Kalas asks: "Could the apparent
discrepancy result from 'planet mania', a bias among astronomers
in which every cavity and blob, even a wiggle, in circumstellar
dust disks is taken as evidence for extrasolar planets? Which
dust-planet relation does theory favor?" 5) Kalas says
theoretical arguments are available for both interpretations: one
can show that gravitational perturbations from a planetary object
will eventually create a cavity in a dust disk, but one can also
show that a planet can create a dust wake that looks like a large
blob following the planet in its orbit. 6) Kalas says: "At
present, therefore, we cannot uniquely identify the cause of the
dust blobs and dust cavities near these four stars. Planet-mass
objects are just one of the physically possible ideas."
QY: Paul Kalas
(Science 10 Jul 98 281:182) (Science-Week 31 Jul 98)
-------------------
Related Background:
EVIDENCE OF A PROTOPLANETARY DISK AROUND A YOUNG STAR
... Since the details of disk formation, and the physical
properties of protoplanetary disks, can be modelled by
quantitative theory, the general idea is to investigate such
disks that are apparent around stars to test the theoretical
models. There is no way to do that with our own solar system,
because the protoplanetary disk is long gone. One needs young
stars. This week Vincent Mannings et al (California Institute of
Technology, CA US) report observations and analysis of the
apparent protoplanetary disk of a star only 6 million years old,
with a mass of 2.3 solar masses. The mass of the disk is
evidently greater than the minimum required to form a planetary
system like our own. QY: V. Mannings
(Nature 7 Aug 97) (Science-Week 15 Aug 97)
3. ON THE BLOCKADE OF THE COSMIC MAP BY OUR OWN GALAXY
In astronomy, the "Great Attractor" is a presumed large
concentration of mass detectable only by its gravitational pull
on our own Galaxy and the local supercluster of galaxies of which
our Galaxy is a member. Our Galaxy is also a member of a subset
of the local supercluster, the "Local Group", a comparatively
small cluster of galaxies with 30 to 40 known members that
includes the Andromeda galaxy (M31) and the Large Magellanic
Cloud. The so-called "zone of avoidance" is a region of the sky
that roughly coincides with the belt of the Milky Way and where
no galaxies are observable due to presence of light-absorbing
clouds in the Galactic plane. ... ... In a review of the
astronomy of galaxies obscured by our own Galaxy, R.C. Kraan-
Korteweg and O. Lahav make the following points: 1) We are
located approximately 28,000 light-years from the center of our
Galaxy in the midst of its disk. Over 20 percent of the universe
is hidden from view, blocked by dust and stars in our own disk,
but during the past few years, astronomers have found methods to
look through the murk and reconstruct the veiled universe from
its effects on those parts that can be seen. 2) Light from other
galaxies penetrates our own Galaxy to varying degrees, depending
on the wavelength of the light. The longest wavelengths, that of
radio and far-infrared radiation, are hardly affected, but
shorter wavelengths such as near-infrared, visible, and
ultraviolet are blocked by the dust and gas clouds within our
Galaxy. For very short wavelengths such as strong x-rays, the
Galactic gas becomes transparent again. 3) In recent work on the
blocked regions of the cosmic map, many new galaxies have been
discovered, including a galaxy so close that it would dominate
our skies were it not obscured by the Galactic disk. New colossal
galaxy clusters have also been discovered, and a first look at
the core of the Great Attractor has been obtained. 4) For
generations of astronomers, the zone of avoidance has been an
obstacle to investigating fundamental issues such as the
formation of our own Galaxy, the origin of the Local Group
motion, the connectivity of chains of galaxies, and the true
number of galaxies in the Universe. Now, as the result of new
techniques, the former zone of avoidance has become one of the
more exciting regions in the extra-Galactic sky, the mysterious
Great Attractor is now well-mapped, and the discovery of a dwarf
galaxy merging with our own Galaxy has provided some evidence
concerning how our Galaxy was formed. In addition, there have
been observations of the vast cosmic filaments of galaxy clusters
that are challenging now theories of dark matter and meta-
galactic structure formation.
-----------
R.C. Kraan-Korteweg and O. Lahav (2 installations, MX UK):
Galaxies behind the Milky Way.
(Scientific American October 1998)
QY: Renee C. Kraan-Korteweg, University of Guanajuato, MX.
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 9Oct98
4. EVIDENCE SUGGESTING FE(III) REDUCTION BY EARLY EARTH BACTERIA
It is generally considered that *sulfur reduction was one of the
earliest forms of microbial respiration, since the known
microorganisms that are most closely related to the last common
ancestor of modern living forms are primarily *anaerobic sulfur-
reducing *hyperthermophiles. Geochemical evidence, however, seems
to indicate that *Fe(III) is more likely than sulfur to have been
the first external *electron acceptor of global significance in
microbial metabolism. ... ... Vargas et al now report that
*Archaea and Bacteria that are most closely related to the last
common ancestor can reduce Fe(III) to Fe(II) and conserve energy
to support growth from this respiration. The authors report that
even *Thermotoga maritima, previously considered to have only
*fermentative metabolism, could grow as a respiratory (oxygen-
utilizing) organism when Fe(III) was provided as an electron
acceptor. The authors suggest these results provide
microbiological evidence that Fe(III) reduction could have been
an important process on early Earth, and that microorganisms
might contribute to Fe(III) reduction in modern hot biospheres.
The authors further suggest that their discovery that
hyperthermophiles that had previously been thought to require
sulfur for cultivation can instead be grown without the
production of toxic and corrosive sulfide should aid biochemical
investigations of these poorly understood organisms.
-----------
M. Vargas et al (4 authors at University of Massachusetts
Amherst, US): Microbiological evidence for Fe(III) reduction on
early Earth.
(Nature 3 Sep 98 395:65)
QY: Derek R. Lovley
-----------
Text Notes:
... ... *sulfur reduction: In general, reduction refers to a
chemical process in which the proportion of electronegative
substituents is decreased, or the charge on an ion is made more
negative, or the oxidation number is lowered.
... ... *anaerobic: refers to a life form or process sustained in
the absence of free (gaseous or dissolved) oxygen.
... ... *hyperthermophiles: In general, microorganisms whose
optimal growth temperature lies above 80 degrees centigrade.
... ... *Fe(III): Refers to the +3 (ferric) oxidation state of
iron. The most stable oxidation state of iron is the ferrous
state (+2).
... ... *electron acceptor: The electron acceptor is the atom or
molecule that is reduced in an oxidation-reduction reaction.
... ... *Archaea: (archaebacteria) One of the 3 apparent domains
of life, along with eukaryotes (eukarya) and eubacteria
(bacteria). But the taxonomic separation of archaebacteria and
eubacteria is opposed by some biologists.
... ... *Thermotoga maritima: A hyperthermophilic group in the
domain of eubacteria, first discovered in the Mediterranean off
the shores of Italy.
... ... *fermentative metabolism: In general, refers to the
breakdown of organic molecules, typically sugars and fats, to
yield simpler organic molecules. The term is often used as a
synonym for anaerobic metabolism.
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Summary & Notes by SCIENCE-WEEK http://scienceweek.com 9Oct98
5. ANTIBODIES SPECIFIC FOR FULLERENES
Fullerenes are large molecules composed entirely of carbon, with
the chemical formula C(n), where n is any even number from 32 to
over 100. They apparently have the geodesic structure of a hollow
spheroidal cage with a surface network of carbon atoms connected
in hexagonal and pentagonal rings. A great deal of research
activity followed the first synthesis of fullerenes in 1985,
including the first synthesis of related structures known as
nanotubes. Fullerenes have also been tested for biological
activity, including antiviral, antioxidant, and *chemotactic
activities. The use of fullerenes as biological or
pharmacological agents requires the measurement of dosage and
serum levels by sensitive and simple immunological procedures,
and this in turn requires that specific *antibodies to fullerenes
be produced. The clonal selection theory proposes that antigens
elicit the production of antibodies by selecting for specific
antibody-producing cells already present in the repertoire of
immunized animals. The idea is that the repertoire is diverse
enough to produce antibodies to any possible molecule. So the
question arises whether the immune system repertoire is complete
enough to recognize and respond to the unprecedented geodesic
structure of the fullerenes or sufficient aspects of it -- in
particular, whether the immune system can process a fullerene-
protein conjugate and display the *processed peptides for
recognition by *T-cells to yield antibodies. ... ... B.-X. Chen
et al now report that immunization of mice with a C(sub60)
fullerene derivative conjugated to a protein (bovine
thyroglobulin) yielded a population of fullerene-specific
antibodies of the *IgG isotype. The authors suggest this
indicates that the immune system repertoire was diverse enough to
recognize and process fullerenes as protein conjugates. The
authors also report that the population of antibodies included a
subpopulation that crossreacted with a C(sub70) fullerene. The
assays used by the authors were made possible by the synthesis of
water-soluble fullerene derivatives, and the authors discuss
possible interactions of fullerenes with the combining sites of
antibodies in the context of the physical chemistry of fullerenes
and previously described protein-fullerene interactions.
-----------
B.-X. Chen et al (5 authors at 2 installations, US): Antigenicity
of fullerenes: Antibodies specific for fullerenes and their
characteristics.
(Proc. Natl. Acad. Sci. US 1 Sep 98 95:10809)
QY: B.F. Erlanger
-----------
Text Notes:
... ... *chemotactic: In general, the term "chemotaxis" refers to
any movement of an organism in response to chemical
concentration
gradients.
... ... *antibodies: An antibody is a protein molecule produced
by the immune system of vertebrate organisms, the molecule
designed to specifically interact with a particular chemical
entity called an "antigen". Antibodies are members of the
immunoglobulin superfamily of glycoproteins and are secreted by
mature vertebrate B-cells (see *T-cells below). In general, an
antigen is any substance (often protein or glycoprotein) that can
be recognized by an already induced immune response and initiate
production of further specific antibody, the antibody binding at
a specific domain of the antigen molecule. In general, the
response of the vertebrate immune system to an antigen involves a
complex cascade of events that includes a discrimination of
foreign protein from self-protein and the proliferation of
special cells that produce antibodies specific for the immune
system-provoking antigen.
... ... *processed peptides: Most antigens are first degraded by
auxiliary immune system cells, and then antigenic peptide
fragments ("processed peptides") are "presented" to T-cells (see
below) with a subsequent proliferation of antigen-specific B-
cells, and production of specific antibodies by these B-cells.
... ... *T-cells: (T-lymphocytes) Lymphocytes (lymph cells,
lympho-leukocytes) are a type of leukocyte (white blood cell)
involved in the immune response. There are two classes of such
lymphocytes: 1) the B-cells, which after a cascade of immune
system events involving a specific antigen change into
proliferating specific antibody producing plasma cells; and, 2)
the T-cells, one subclass of which (cytotoxic T-cells) interacts
directly with foreign invaders such as bacteria and viruses,
while the other subclass of T-cells (helper T-cells) is involved
in the proliferation of antibody-specific B-cells.
... ... *IgG isotype: Antibodies are immunoglobulin (Ig)
proteins, of which their are 5 subclasses: IgA, IgD, IgE, IgG,
IgM. In this context, an "isotype" is an antigenic marker
(surface protein) that occurs in all members of an immunoglobulin
subclass.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 9Oct98
-------------------
Related Background:
NEW EVIDENCE CONCERNING EVOLUTION OF THE IMMUNE SYSTEM
*Lymphocytes of the *vertebrate adaptive immune system rely on an
array of variable *immunoglobulin (antibody) and *T-cell *antigen
*receptors for specific recognition of antigens. In the genome,
the genes encoding the variable portions of these receptors are
typically split into variable components (V), joining components
(J), and in some cases, diversity gene components (D). One of
each type of each component or gene segment is joined together in
a site-specific *recombination reaction to form the *exon that
encodes the antigen-binding portion of the polypeptide that forms
the antibody or T-cell receptor. This reaction, known as V(D)J
recombination, occurs only in lymphocytes, and in some vertebrate
species is responsible for generating much of the diversity seen
in antigen receptors. It is known that the two proteins encoded
by the recombination-activating genes RAG1 and RAG2 are
essential to the V(D)J recombination reaction, the proteins
mediating sequence-specific DNA recognition of recombination
"signals" (specific short base-pair sequences involved in this
particular recombination process) and DNA cleavage next to these
signals. ... ... Agrawal et al report that in vitro the proteins
RAG1 and RAG2 together form a *transposase capable of excising a
piece of DNA containing recombination signals from a donor site
and inserting the excised piece into a target DNA molecule. The
products formed contain a structure similar to that created by
*retroviral integration and by all known *transposition
reactions. The authors point out that all jawed vertebrates
studied thus far possess adjacent RAG1 and RAG2 genes as well
as immunoglobulin and T-cell receptor genes, which usually must
be assembled by *somatic recombination before they can be
expressed. There is no evidence that any of these molecules, or
antigen-specific lymphocytes, are found in jawless vertebrates
(hagfish and lamprey) or invertebrates. This indicates that split
antigen-receptor genes and the enzymatic machinery necessary for
their assembly into functional units arose in the approximately
100 million years between the divergence of jawless and jawed
vertebrates and the divergence of cartilaginous and bony fishes.
The authors suggest their results are evidence in favor of the
theory that a pivotal event in the evolution of the antigen-
specific immune system was the insertion of a "RAG *transposon"
into the genome of a vertebrate ancestor.
-----------
A. Agrawal et al (Yale University, US): Transposition mediated by
RAG1 and RAG2 and its implications for the evolution of the
immune system. (Nature 20 Aug 98 394:744)
QY: David G. Schatz
-----------
Text Notes:
... ... *Lymphocytes: These are a type of leukocyte responsible
for the immune response. There are two classes of lymphocytes: 1)
the B-cells, which when presented with an activating chemical
entity (antigen) change into antibody producing plasma cells;
and, 2) the T-cells, which interact directly with foreign
invaders such as bacteria and viruses. There are also forms of T-
cells that are involved with B-cell activation.
... ... *vertebrate adaptive immune system: The term "adaptive"
here refers to those parts of the immune system that are capable
of adaptation to chemical experience.
... ... *immunoglobulin (antibody): In general, antibodies are
immunoglobulin proteins.
... ... *T-cell: see *Lymphocyte note above.
... ... *antigen: Any chemical entity that activates an immune
response, especially an entity originating outside the body.
... ... *receptors: In this context, cell surface macromolecules
that bind antigens.
... ... *recombination: In general, integration of DNA fragments
into a particular site in a genome.
... ... *exon: In general, any DNA sequence encoding and giving
rise to a translated polypeptide sequence.
... ... *transposase: Any enzyme required for the transposition
of DNA segments (see below, *transposition reactions).
... ... *retroviral integration: Retroviruses are single-stranded
RNA viruses that have an enzyme called reverse transcriptase, and
with this enzyme the viral RNA is used as a template to produce
viral DNA from cellular material. This DNA is then incorporated
(integrated) into the host cell's genome, where it codes for the
synthesis of viral components.
... ... *transposition reactions: In general, any reactions that
insert or excise DNA fragments into or from a genome.
... ... *somatic recombination: Somatic cells are any cells other
than germ cells (gametes). Somatic recombination, where it
occurs, involves the transposition of DNA fragments from one DNA
molecule to another, or within the same DNA molecule. Somatic
recombination theory is one of the theories proposed to explain
the enormous variety of antibodies produced by the immune system.
... ... *transposon: A large transposable genetic element having
at least the genes necessary for its own transposition to the
same or another genome.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 18Sep98
-------------------
Related Background:
AN ANALYSIS OF HYPERMUTATION ANTIBODY GENE TARGETS
In vertebrates, the immune system provides protection against
foreign agents, for the most part by recognizing molecular
entities (antigens) that are interpreted by the immune system as
of foreign origin. Many types of cells are involved in the immune
response, with 3 primary types the so-called B-cells, cytotoxic
T-cells, and helper T-cells. In general, cytotoxic T-cells
recognize and kill host cells that are infected, while B-cells
are cells that secrete antibodies, protein molecules that bind to
antigens. Helper T-cells (and other immune system cells) are
involved in both processes, provoking particular steps in the
immune response. The ability of the immune system to recognize
and respond to the enormous number of antigens encountered by an
individual in a lifetime is due in large part to the diversity of
antibodies (also called *immunoglobulins) produced by B-cells.
Each B-cell produces only a single species of antibody, and
during the systemic immune response, the presence of a specific
antigen results in the proliferation by *clonal selection of
B-cells producing antibody specific for that antigen. All
antibody molecules are proteins consisting of two light
polypeptide chains and two heavy polypeptide chains that are
joined together by disulfide bonds. Each polypeptide chain
contains regions of variable amino acid sequence and regions of
constant amino acid sequence, resulting in an antigen-binding
locus with a variable specific affinity for particular ligands.
Further antibody variability arises from a variability in the way
the particular segments of the antibody are joined. The ability
of antibodies to recognize a large variety of antigens is thus
controlled, in part, by the variability of the variable segments
of the amino acid sequences of the antibody polypeptide chains.
This amino acid variability in the light and heavy chains is the
result of a variability in B-cell DNA generated by somatic
recombination, an alteration and reassembly of genes. During the
past 15 years, it has become evident that in immune system B-
cells, the part of the genome coding for the variable parts of
antibodies is involved in a process of "hypermutation", a
substantial increase in mutation rate, the effect of which is to
provide the immune system with a rapidly changing enormous
library of possible antibodies. This hypermutation process is
highly specific to the immune system, and it occurs only within a
DNA segment of approximately 1000 to 2000 DNA bases, the segment
that encodes the bulk of the variable regions of the antibody
polypeptides. The mechanism of the hypermutation process remains
unknown. ... ... Milstein et al (3 authors at Medical Research
Council, UK) report an analysis of the average frequency of
mutations of each of the 3 bases of all *nucleotide triplets in
the relevant DNA segment. Their focus was the question of whether
the B-cell hypermutation process involves one strand or both
strands of the DNA double helix. Many hypermutation models
propose that only one of the strands of DNA is involved in
hypermutation. The Milstein et al analysis used large databases
of mutations involving both variable and non-variable mutation
targets. The essential idea is that by using large databases of
such mutations, one can contrast the mutation distributions
observed with what would be expected if either one or both DNA
strands are hypermutation targets. The authors report their
analysis indicates there are two aspects of the hypermutation
process, one aspect that is DNA strand-dependent and the other
aspect that is not. The strand-independent aspect is sensitive to
local DNA sequences (i.e., mutation hot spots correlate with
local sequence environments), but without strand preference. The
authors report a similar conclusion has been reached by a
separate research group (Dorner et al, Immunol Rev. 162:161
1998).
QY: Cesar Milstein, Medical Research Council Laboratory of
Molecular Biology, MRC Centre, Hills Road, Cambridge CB2 2QH, UK.
(Proc. Natl. Acad. Sci. US 21 Jul 98 95:8791)
(Science-Week 21 Aug 98)
-------------------
Related Background:
... ... *immunoglobulins: The immunoglobulins are a large
glycoprotein category that includes antibodies as a subset.
... ... *clonal selection: In this context, the process by which
an antigen selectively stimulates the proliferation of those
B-cells that possess antigen receptors targeted against the
stimulating antigen.
... ... *nucleotide triplets: Nucleotides are molecules
consisting a purine or pyrimidine base joined to a 5-carbon sugar
(ribose or deoxyribose) containing an attached phosphate group.
Nucleotides are the fundamental building blocks of nucleic acids,
and nucleotide triplets of 3 contiguous nucleotides are the
fundamental coding units of the genome.
6. ON PEPTIDE NUCLEIC ACIDS
A peptide nucleic acid is a nucleic acid analog in which the
entire phosphate sugar backbone has been replaced by an uncharged
polyamide backbone, the side groups consisting of the nitrogenous
purine and pyrimidine bases found in biological nucleic acids.
Such molecules are known to bind to single-stranded DNA. Peptide
nucleic acids mimic DNA but are more stable and may have the
potential to substitute for DNA in diagnostic and therapeutic
applications. When transcription of the DNA genome occurs, the
enzyme RNA polymerase catalyzes the formation of a "messenger"
RNA (mRNA) complementary to a segment of one of the strands of
the double-stranded DNA genome. Considering double-stranded DNA,
"antisense" DNA refers to the DNA strand opposite to the strand
that is transcribed into messenger RNA and subsequently
translated into protein. Thus, in principle, the artificial
introduction into the cell of antisense DNA complementary to a
particular messenger RNA could result in the binding of the
antisense DNA to the complementary messenger RNA, and that
binding could prevent the subsequent translation of RNA code into
the synthesis of the protein for which the messenger RNA was
encoded. This idea has become the basis of what is called
"antisense therapy", which essentially involves an
oligonucleotide or an oligonucleotide analog designed by its
sequence to bind to the messenger RNA transcribed from a specific
gene whose expression is pathogenic. Examples of such genes are
oncogenes responsible for the development of cancer. Analogous to
antisense therapy, is "antigene" therapy, which involves the
binding of an artificially introduced complementary sequence
segment to a specific sequence in the double-stranded DNA genome,
with a consequent blockade of transcription of the specific gene.
Antigene therapy thus bypasses messenger RNA and involves a
direct binding to the genome. ... ... In a review of peptide
nucleic acids and their possible use in therapy, P.E. Nielsen
makes the following points: 1) Peptide nucleic acid oligomers
bind more strongly and more specifically than DNA itself to
either DNA or RNA molecules with complementary base sequences. 2)
Peptide nucleic acids are relatively easy to synthesize, and they
show excellent chemical and biological stability. 3) Peptide
nucleic acids bind efficiently and with high sequence selectivity
to double-stranded DNA, the binding apparently involving strand
displacement -- opening of the DNA double helix and binding to
only one of the DNA strands. 4) The author suggests that the
properties of peptide nucleic acids make this type of molecule a
prime candidate for the basis of future antisense and antigene
agents, and that studies in cell-free systems and animal cell
culture systems have already demonstrated good antisense and
antigene activity of peptide nucleic acids.
-----------
P.E. Nielsen (University of Copenhagen, DK): Peptide Nucleic
Acids.
(Science & Medicine Sep/Oct 1998)
QY: Peter E. Nielsen
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 9Oct98
-------------------
Related Background:
ACTION OF PEPTIDE NUCLEIC ACIDS TARGETED TO RIBOSOMAL RNA
... Ribosomal RNA (rRNA) is a class of RNA molecules that have an
important role in the structure of ribosomes, the large molecular
entities that carry out protein synthesis in all cells.
Transcription is the process by which genetic information in DNA
code is converted into RNA code, and translation is protein
synthesis, the process during which polypeptides are synthesized
on ribosomes in accordance with RNA code. Agar plates are
solidified nutrient gel plates used for laboratory surface
cultures of microorganisms. ... ... Good and Nielsen (University
of Copenhagen, DK) report that peptide nucleic acids targeted to
functional and accessible sites in ribosomal RNA can inhibit
translation in a bacterial (E. coli) cell-free transcription-
translation system, with 50% reductions caused by nanomolar
concentrations. The effect in vitro is quantitatively similar to
that of the known translation inhibitor and antibiotic
tetracycline. In addition, the targeted peptide nucleic acids
inhibited bacterial growth on agar plates and in liquid culture.
The authors suggest their results demonstrate that ribosomal RNA
is a possible target for sequence-designed novel antibiotics
based on DNA analogues or mimics.
QY: P.E. Nielsen
(Proc. Natl. Acad. Sci. US 3 Mar 98)
(Science-Week 27 Mar 98)
-------------------
Related Background:
TARGETED MUTAGENESIS BY PEPTIDE NUCLEIC ACIDS
... Fibroblasts are a type of connective tissue cell, secreting
structural proteins (e.g., collagen) that form certain tissue
components, including the extracellular matrix. In this report,
the term "clamp" refers to a binding of a DNA strand with a DNA
segment "clamped" between 2 segments of peptide nucleic acid. ...
... Faruqi et al (3 authors at 2 installations, US) report the
design of peptide nucleic acids to bind as clamps to a specific
chromosomal gene site in mouse fibroblasts, with an induction of
mutations 10-fold above the background. DNA sequence analysis
revealed the majority of the mutations were located within the
peptide nucleic acid binding site and the mutations consisted
mostly of single base pair insertions and deletions. The authors
suggest that the technique provides a high affinity peptide
nucleic acid clamp that constitutes a mutagenic lesion that may
provoke replication errors, and that the ability to direct
mutations to a target site in chromosomal DNA by using peptide
nucleic acids may be a useful tool for research and therapeutic
applications.
QY: Peter M. Glazer
(Proc. Natl. Acad. Sci. US 17 Feb 98)
(Science-Week 3 Mar 98)
7. RNA-CATALYZED NUCLEOTIDE SYNTHESIS
In research concerning the origin of life on Earth, the "RNA
world" hypothesis proposes that early life developed by making
use of RNA molecules, rather than proteins, to catalyze the
synthesis of important biological molecules. It is believed,
however, that the nucleotides constituting RNA were scarce on
early Earth, so that RNA-based life must have acquired the
ability to synthesize RNA nucleotides from simpler and more
readily available precursors such as sugars and bases. Apparently
plausible prebiotic synthesis routes have been proposed for
sugars, sugar phosphates, and the 4 RNA bases, but the coupling
of these molecules into nucleotides, specifically pyrimidine
nucleotides, poses a challenge to the RNA world hypothesis.
... ... P.J. Unrau and D.P. Bartel report the application of in
vitro selection to isolate RNA molecules that catalyze the
synthesis of a pyrimidine nucleotide at their *3' terminus. The
authors suggest the finding that RNA can catalyze this type of
reaction, which is modeled after pyrimidine synthesis in
contemporary metabolism, supports the idea of an RNA world that
included nucleotide synthesis and other metabolic pathways
mediated by *ribozymes.
-----------
P.J. Unrau and D.P. Bartel (Massachusetts Institute of
Technology, US): RNA-catalyzed nucleotide synthesis.
(Nature 17 Sep 98 395:260)
QY: David P. Bartel, Mass. Inst. of Technology 617-253-1000.
-----------
Text Notes:
... ... *3' terminus: Both DNA and RNA are polymers whose
constituent nucleotides are linked by 3',5'-phosphodiester bonds,
and the polymers have polarity, with one end a 5'-end unattached
and the other end a 3'-end unattached. This asymmetry is
mirrored
in the differing functional involvement of the 2 ends in various
biochemical events in the living cell.
... ... *ribozymes: First discovered in 1981, ribozymes (not to
be confused with riboSOMES) are a small group of RNA molecules
that act as enzymes. They are found in the ciliate protozoan
Tetrahymena, and they are intriguing because they defy the usual
rule that enzymes are proteins.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 9Oct98
-------------------
Related Background:
IN VITRO PEPTIDE BOND FORMATION BY SELECTED RIBOZYMES
Ribozymes are a small group of RNA molecules that act as enzymes.
They were first discovered by Thomas Cech in the 1980s in the
ciliate protozoan Tetrahymena, and they are intriguing because
they defy the usual rule that enzymes are proteins. A ribosome
(not to be confused with riboZYME) is a small particle, a complex
of various ribonucleic acid component subunits and proteins that
functions as the site of protein synthesis, and peptidyl trans-
ferase is a ribosomal component that catalyzes peptide bond
formation, which is the chemical reaction involved in the
synthesis of new protein molecules. Transcription is the process
by which genetic information in DNA is converted into RNA, and
reverse transcription, involving the enzyme reverse transcript-
ase, is the synthesis of complementary DNA from an RNA template.
In current molecular biology, "selection" is the term used to
described an in vitro synthetic procedure whereby a particular
nucleic acid reactive sequence is derived from an initial large
pool of possibilities by repeated cycles of reaction/isolation/
reverse transcription/amplification/transcription. Zhang and Cech
(University of Colorado Boulder, US) now report the in vitro
selection of ribozymes (196 nucleotides) that perform the same
peptidyl transferase reaction as the ribosome, i.e., the
ribozymes can join amino acids by a peptide bond. The authors
suggest that study of the mechanism of peptidyl transfer by in
vitro selected ribozymes may help reveal the molecular details of
ribosome-catalyzed protein synthesis.
QY: Thomas R. Cech
(Nature 6 Nov 97) (Science-Week 28 Nov 99)
-------------------
Related Background:
MAGNESIUM ION CORE DETERMINES AN RNA FOLDING ARCHITECTURE
... In general, much more is known about the final folding
architecture of proteins than about the final folding architect-
ure of molecules like RNA. Final folding architecture in proteins
is important because a specific architecture is essential for
enzymatic activity. Now here are ribozymes, which are not
proteins, but which also have high-level folding and which are
also enzymes. This month Jamie H. Cate et al (Yale University,
US) report that the x-ray crystal structure of a major domain of
a large ribozyme (the Tetrahymena group I intron P4-P6) reveals
the molecule folds around a core of magnesium ions. At the center
of the domain, five magnesium ions are bound at a junction where
three RNA helices join, and single-atom changes in any four of
the five sites destroys the folding pattern of the entire domain.
So the ribozyme final folding architecture, like that of many
enzymatic proteins, depends on a metal cofactor. If one puts
together this information with that of the previous report on
metallo-enzymes, one gets a glimmer that the future rational
design of biological macromolecular configurations will not be
limited to proteins.
(Nature Structural Biology 4:553 1997) (Science-Week 10 Jul 97)
8. LOCALIZATION OF SOUND BY EARLY-BLIND HUMAN SUBJECTS
There are currently two experimentally-based views concerning the
question of whether blind persons develop capacities of their
remaining senses that exceed those of sighted individuals. One
view proposes that blind individuals are severely impaired
because vision is so essential in the development of spatial
concepts. The second view proposes that compensation occurs
through the remaining senses, allowing blind individuals to
develop an accurate concept of space. ... ... N. Lessard et al
report a study of 3-dimensional spatial mapping by early-blind
individuals with or without residual vision. Four groups were
tested: totally blind subjects (n = 8); blind subjects with
residual vision in the peripheral field (n = 3); normally sighted
but blindfolded controls (n = 7); sighted controls (n = 29).
Subjects were asked to localize a sound source in the horizontal
plane, the sounds delivered randomly through 16 loudspeakers
mounted on a semicircular perimeter. Subjects were tested under
monaural and binaural listening conditions. The authors report
the following: 1) early-blind subjects can map the auditory
environment with equal or better accuracy than sighted subjects;
2) Unlike sighted subjects, early-blind subjects can correctly
localize sounds monaurally; 3) blind individuals with residual
peripheral vision localized sounds less precisely than sighted or
totally blind subjects, confirming that compensation varies
according to the etiology and extent of blindness. The authors
suggest their results resolve a long-standing controversy by
providing behavioral evidence that totally blind individuals have
better auditory ability than sighted subjects, enabling them to
compensate for their loss of vision.
-----------
N. Lessard et al (4 authors at University of Montreal, CA):
Early-blind human subjects localize sound sources better than
sighted subjects.
(Nature 17 Sep 98 395:278)
QY: F. Lepore
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 9Oct98
9. BIOLOGICAL ACTION OF LEPTIN AS AN ANGIOGENIC FACTOR
Angiogenesis is the generation of new blood vessels, a controlled
sequence of cell differentiation and tissue formation programmed
by the genome. It is of obvious importance during embryological
development, since new tissues need a blood supply in order to
continue macroscopic growth, and the angiogenesis process is also
of great importance during tissue trauma repair. Like new
embryological tissue, a neoplasm (a tumor) also needs a blood
supply, and one of the characteristics of tumor growth is the
provocation of angiogenesis by the cancer cells so that the mass
of such cells becomes supplied with adequate vascularization. It
is known, for example, that tumors will not grow beyond a few
millimeters in diameter in the absence of a newly forming blood
supply. Cancer cells apparently provoke angiogenesis by secreting
growth factor substances, and if this is prevented, tumor growth
will be severely limited. Leptin is a recently discovered
circulating hormone secreted by *adipocytes (fat cells). The
hormone influences body weight *homeostasis through effects on
food intake and energy expenditure. It also modulates other
physiological actions, including lipid metabolism,
*hematopoiesis, *pancreatic beta-cell function, ovarian function,
and *thermogenesis. Despite this multiplicity of effects in
tissues outside the nervous system, the leptin receptor is
expressed predominantly in the *hypothalamus. One apparent
variant of the leptin receptor is a trans-membrane protein (OB-
Rb) expressed at high levels in discrete hypothalamic regions,
and evidence indicates this leptin receptor has a *cytoplasmic
domain that transduces the *leptin signal via the *Jak-STAT
pathway. The current consensus is that adipose tissue mass is
regulated by a hormone (possibly leptin) produced by adipocytes
and released into the bloodstream. This implies a plastic
microvascular bed that can provide an adequate blood supply for
new adipose tissue and be capable of undergoing adaptive changes
required by physiological or pathological fluctuations in
adiposity. ... ... M.R. Sierra-Honigmann et al now report that
the leptin receptor OB-Rb is expressed in human blood vessels and
in primary cultures of human *endothelial cells, and that in
vitro and in vivo assays reveal that leptin has angiogenic
activity. The authors suggest their observations indicate that
the vascular endothelium is a target for leptin, that leptin-
induced angiogenesis may facilitate increased energy expenditure,
and that leptin, acting as a functional link between adipocytes
and the vasculature, might also play an important extra-
hypothalamic and localized role in the modulation of adipose
tissue mass.
-----------
M.R. Sierra-Honigmann et al (11 authors at 3 installations, US):
Biological action of leptin as an angiogenic factor.
(Science 11 Sep 98 281:1683)
QY: M. R. Sierra-Honigmann
-----------
Text Notes:
... ... *adipocytes: These are fat cells in connective tissue,
each cell containing one or more fat globules that compress the
cytoplasm of the cell into a thin envelope. The fat globules are
essentially energy storage bins.
... ... *homeostasis: The term "homeostasis" refers to a
physiological equilibrium necessary in general for the viability
of an organism, and in particular for the operation of many
cellular functions. Homeostatic mechanisms in biological systems
usually involve an element of negative feedback signaling. In
vertebrates, for example, when blood temperature is too high,
temperature receptors provoke a sequence of events involving many
pathways that ultimately results in a lowering of body temper-
ature. Similar homeostatic mechanisms operate at cellular levels.
... ... *hematopoiesis: (hemopoiesis, hematogenesis) Refers to
the formation and development of the various types of blood
cells.
... ... *pancreatic beta-cell: These are the pancreatic cells
that secrete the hormone insulin.
... ... *thermogenesis: In this context, the physiological
process of heat production in the body.
... ... *hypothalamus: A deep brain structure with various
clusters of nerve cells controlling several important homeostatic
functions such as temperature regulation and food intake, and in
addition the sex drive, aggressive emotions, psychosomatic
effects, etc. The hypothalamus essentially integrates the
activity of the autonomic nervous system, and it acts as an
intermediary between the endocrine (hormone) system and the
nervous system, with various hypothalamic neuron types secreting
hormones themselves. In general, the term "hormones" refers to
chemical messengers which are distributed systemically via the
bloodstream.
... ... *cytoplasmic domain: A "trans-membrane" protein receptor
essentially has 3 domains: extracellular, membrane, and
cytoplasmic (intracellular). In other words, the protein extends
completely through the plasma membrane, protruding from the outer
surface and inner surface of the membrane. The outer protrusion
apparently acts as a receptor for an extracellular ligand (e.g.,
a hormone), the binding of ligand and receptor providing a
"signal" that causes some alteration in the other end of the
protein, the protrusion of the protein into the cytoplasm. This
alteration in turn provokes a cascade of intracellular chemical
interactions that result in a signal transmitted to one or more
intracellular genetic or physiological control centers.
... ... *leptin signal: Refers to the "signal" (ultimate effect
on some intracellular control mechanism) produced by the binding
of leptin as a ligand to its membrane receptor.
... ... *Jak-STAT pathway: The term "STATs" refers to signal
transducers and activators of transcription, and together with
enzymes known as Janus kinases they mediate the signaling
mechanism known as the JAK-STAT pathway, which is known to
provoke the transcription of certain regulated genes.
("Transcription" is the process by which genetic information in
DNA is converted into RNA.)
... ... *endothelial cells: Flat cells forming a layer lining
blood vessels, lymphatic vessels, the heart, etc.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 9Oct98
-------------------
Related Background:
FIRST IDENTIFICATION OF MOUSE OBESITY GENE IN HUMANS
In 1994 an obesity gene and its protein product (leptin), were
discovered in obese mice. It has been determined that a defect in
the gene causes a severe reduction in the output of functional
leptin by fat cells (adipocytes). Leptin apparently acts as a
messenger to the hypothalamus in the brain, the absence of the
protein causing excessive eating behavior without satiation. Now
a similar gene has been discovered in humans, this gene also
responsible for the production of leptin by human adipocytes.
Carl T. Montague et al (15 authors at various installations, UK)
studied a homozygous genetic defect in two children suffering
from extreme obesity, and have isolated and characterized the
gene, and related it to the previously identified mouse gene
known as ob/ob. As in mice, the result of a defect in the gene is
an order of magnitude reduction in the circulating blood
concentration of the protein leptin. The results do not mean that
all instances of obesity in humans are produced by defects in
this gene, but certainly a new area of research into the
molecular genetics of human obesity has now been defined. In
addition, the authors offer the hope that recombinant human
leptin may be found to correct leptin deficiency in clinical
cases. (Nature 26 Jun 97) (Science-Week 3 Jul 97)
10. ANGIOGENESIS: INHIBITION BY NEOMYCIN
The protein angiogenin is a potent inducer of neovascularization
(angiogenesis). Angiogenin was first isolated from tumor-
conditioned culture medium in the 1980s in the course of a search
for tumor angiogenesis agents. Binding of angiogenin to
*endothelial cells activates the enzyme phospholipase C (an
enzyme that causes the degradation of phospholipids), activates
cell migration and invasion, activates cell proliferation, and
activates cell differentiation. A striking feature of angiogenin
is that it normally circulates in human plasma at a concentration
of 250 to 360 nanograms per milliliter. Plasma angiogenin may
promote wound healing when it leaves blood vessels (for example,
as a result of tissue trauma). However, circulating angiogenin
would be a major obstacle for anti-angiogenin therapies that
attempt to neutralize angiogenin to suppress unwanted
angiogenesis. It is known that angiogenin is taken up by
endothelial cells and translocated to the endothelial cell
nucleus, and that this translocation is essential for
angiogenesis. ... ... G. Hu now reports that neomycin, an
aminoglycoside antibiotic and a known phospholipase C inhibitor,
is also a potent inhibitor of nuclear translocation of angiogenin
and of angiogenin-induced cell proliferation and angiogenesis.
Other aminoglycoside antibiotics, including gentamcin,
streptomycin, kanamycin, amikacin, and paramomycin, have no
apparent effect on angiogenin-induced cell proliferation.
Furthermore, neomycin completely inhibits angiogenin-induced
angiogenesis in the chicken *chorioallantoic membrane at a dose
as low as 20 nanograms per egg. The author suggests these results
indicate that neomycin and its chemical analogs offer potential
as a new class of anti-angiogenin agents that might augment the
agents available for the clinical treatment of angiogenesis-
related diseases.
-----------
G. Hu (Harvard University, US): Neomycin inhibits angiogenin-
induced angiogenesis.
(Proc. Natl. Acad. Sci. US 18 Aug 98 95:9791)
QY: Guo-fu Hu
-----------
Text Notes:
... ... *endothelial cells: Flat cells forming a layer lining
blood vessels, lymphatic vessels, the heart, etc.
... ... *chorioallantoic membrane: An extra-embryonic membrane.
In avian embryos such as that of the chicken, it is fused with
the egg shell and is crucial for chick embryonic development.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 9Oct98
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