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ScienceWeek
SCIENCE-WEEK - Part 1/3
A Free Weekly Digest of the News of Science
March 6, 1998
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"What is the path? There is no path."
-- Niels Bohr
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Contents of This Issue:
Part 1:
1. Present and Future US Physics PhDs Discouraged by Lack of Jobs
2. On the Role of Science in Developing Countries
3. On Irregular Arrays and Randomization
4. Magnetic-Electric Aharonov-Bohm Effect in Metal Rings
5. Direct Observation of Heterogeneous Atmosphere Chemistry
6. Global Warming: On Errors in Predicting Species Range Shifts
7. Use of Coulomb Explosion to Observe Femtosecond Reactions
Part 2:
8. Using DNA as a Template for Assembling a Wire Connection
9. A Study of Protein Hydration in the Gaseous Phase
10. A Mathematical Model of Dynamical Principles in Bio-Processes
11. A Unified View of Polymer Nearest-Neighbor Thermodynamics
12. Single Secretory Vesicles Probed by Capillary Electrophoresis
13. Genetic Interference by Double-Stranded RNA in C. Elegans
14. Targeted Mutagenesis by Peptide Nucleic Acids
Part 3:
15. Collapse of Plasmid DNA into Stable Virus-Like Particles
16. Bcl-2 Prevents Apoptosis by Proton Flux Regulation
17. Use of Caged Peptides to Reveal Cell Signaling Pathways
18. Malaria: Genetics of Host-Parasite Coevolution
19. On Cellular Responses to Interferons and Other Cytokines
20. Farnesyl Transferase Inhibitors as Anti-Tumor Agents
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1. PRESENT AND FUTURE US PHYSICS PHDS DISCOURAGED BY LACK OF JOBS
The American Institute of Physics 1996 Initial Employment Report
has been released, and the facts as presented are apparently
producing gloom in the physics student community. In the year
1995-1996, about 400 temporary and permanent faculty jobs in
physics in the US were filled in all degree-granting institut-
ions, and about 90% of these new placements were drawn from the
ranks of experienced physicists from industry or other univers-
ities. In other words, only about 50 tenure-track jobs in physics
each year are actually open to new graduates and postdocs. And
how many are being trained each year? In 1995-96, 1438 new PhDs
in physics were granted in the US. So the situation at present is
apparently that 97% of new PhDs in physics in the US cannot
expect to find a tenure-track position in a university physics
department, and of those who do find other employment, most of
them find it outside physics in areas such as engineering and
computer software. An American Physical Society poll indicates
that, at the moment, 40% of the junior members of the physics
community "would not advise someone to pursue a career in phys-
ics." This is, perhaps, an example of an endemic problem in Amer-
ican higher education, especially in the sciences and medicine.
The paradigm of sequential events is usually as follows: 1) a
glut of Phds (or MDs); 2) a reduction in the number of Phds (or
MDs) trained; 3) a scarcity produced by the reduction in trained
people; 4) an increase in the number of Phds (or MDs) trained; 5)
a glut of PhDs (or MDs); and so on -- with a complete cycle
usually running about 20 years. In the large, society can perhaps
tolerate this typical result of the operation of oscillating
market forces. In the small, where the security and life fulfill-
ment of individual junior scientists are involved, the result
may
be intolerable. QY: James Glanz
(Science 20 Feb 98)
2. ON THE ROLE OF SCIENCE IN DEVELOPING COUNTRIES
It is natural for nations seeking industrial development in order
to improve their circumstances to attempt to accomplish their
goals in a short time by rational design. But which rational
design? Since in this area of endeavor there exist neither
controlled experiments nor model historical experiences, the
question of choosing the proper road for accelerated development
is not easily answered in either the general case or the specific
case of any particular nation. In an essay on the role of
science
in development, Jose Goldemberg, a physical scientist and
Brazilian government science policy administrator, points out
that after World War II, a small technical elite arose in
developing countries, an elite educated as scientists in the
industrialized world, who believed that by promoting large
enterprises in nuclear energy, electronics, pharmaceuticals, or
space research they could leap-frog the low level of development
of their countries. Goldemberg says that what his scientist
colleagues and national leaders alike failed to understand was
that industrial development does not necessarily coincide with
the possession of nuclear weapons or the capability to launch
satellites. Instead, development requires modern agriculture,
industrial systems, and education, and mere spin-offs from
nuclear energy or space programs will not convert underdeveloped
countries into 20th century industrialized states: the social
infrastructure changes required are fundamental and not
peripheral. In conclusion, Goldemberg suggests that the
transition of a country from developing to developed is a complex
process that demands facing up to the established interests in
society, and the impetus for this must come from all social
sectors. QY: Jose Goldemberg, Institute of Electronics and
Energy, Univ. of Sao Paulo, BR (Science 20 Feb 98)
3. ON IRREGULAR ARRAYS AND RANDOMIZATION
Although the idea of random arrangements of points in planar
arrays arises in many scientific problems, there has been no
useful algorithmic formulation of the extent or degrees of
irregularity of planar arrangements for either finite or infinite
arrays. In the context of this report, the term "vector versions
of approximate entropy" refers to a set of mathematical
statements that define the degree of disorder of an array in
terms of a vector space, and the phrase "combinatorial terms"
refers to combinatorial theory, which is the branch of
mathematics that studies the arrangement of elements into sets.
... ... Singer and Pincus (Princeton University, US) report a
mathematical approach to the unambiguous definition of irregular
or "random" arrangement and the process of randomization itself,
the approach involving vector versions of approximate entropy to
quantify the degree of irregularity of planar (and higher
dimensional) arrangements, with selection rules defining
randomization in strictly combinatorial terms rather than with a
probability-theoretic formulation. The authors suggest extensions
to broad classes of designs, and a diverse range of scientific
applications, including lattice-based models in physics, and
signal detection in seismology and cardiac physiology. QY: Burton
H. Singer
(Proc. Natl. Acad. Sci. US 17 Feb 98)
4. MAGNETIC-ELECTRIC AHARONOV-BOHM EFFECT IN METAL RINGS In
quantum mechanics, the Aharonov-Bohm effect occurs when a beam of
electrons, split into two beams that travel in opposite
directions around a region containing a magnetic flux, are then
recombined with the result that the intensity of the recombined
electron beam oscillates periodically as the enclosed magnetic
field is varied. In general, a tunnel junction is a junction
(potential barrier) involving a thin separation between two
conductors, with the width of the junction equal to or less than
the wavelength of the conductance entity (e.g., the wavelength of
the electron). The essential result at a tunnel junction is that
the conductance entity can penetrate the barrier by means of
quantum mechanical "tunneling", this tunneling effect essentially
arising from the fact that with the wavelength of the particle
larger than the width of the barrier, the particle has a finite
probability, as calculated from its wave-equation, to be on both
sides of the barrier at any instant. The term "quantum interfer-
ence" refers to an amplitude variation resulting from a superpos-
ition (addition) of wave-functions. ... ... Van Oudenaarden et al
(4 authors at 2 installations, NL FR) report observations of the
Aharonov-Bohm effect in metal rings whose metallic continuity is
broken by tunnel junctions, and measurements of quantum interfer-
ence of electrons in this system under the influence of both
magnetic and electrostatic potentials. The authors suggest these
two potentials play interchangeable roles in this system, and
that this type of experiment enables the direct measurement of
the average diffusion time of electrons in metals. QY: Alexander
van Oudenaarden (Nature 19 Feb 98)
5. DIRECT OBSERVATION OF HETEROGENEOUS ATMOSPHERE CHEMISTRY
In chemistry, the term "heterogeneous" refers to a mixture of
phases (e.g., solid-gas or liquid-gas), and a "heterogeneous
chemical reaction" is any reaction involving entities from two
different phases. The term "troposphere" refers to the lowest 10
to 20 kilometers of the atmosphere (with the lower boundary the
surface of the Earth). "Aerosol time-of-flight mass spectrometry"
is a technique for determining the size and chemical composition
of single particles, and by sampling many particles consecut-
ively, the properties of a particle mixture can be defined as it
changes over time. The essentials of the technique involve 1)
accelerating the particle to a terminal velocity determined by
its mass; 2) measuring the velocity (from which the mass is
calculated); 3) laser desorption and ionization of the particle;
4) analysis of the ions to determine the chemical composition of
the desorbed species. ... ... Gard et al (12 authors at 2 instal-
lations, US) report a study of the heterogeneous replacement of
chloride by nitrate in individual sea-salt particles in the
troposphere, the procedure involving continuous monitoring over
time with the use of aerosol time-of-flight mass spectrometry.
Modeling calculations show that the observed chloride displace-
ment process is consistent with a heterogeneous chemical reaction
between sea-salt particles and gas-phase nitric acid, leading to
sodium nitrate production in the particle phase, accompanied by
liberation of gaseous HCl from the particles. The authors suggest
such single-particle measurements, combined with a single-
particle model, make it possible to monitor and explain hetero-
geneous gas/particle chemistry as it occurs in the atmosphere,
and provide a new approach to the study of atmospheric chemistry.
QY: Kimberly A Prather
(Science 20 Feb 98)
6. GLOBAL WARMING: ON ERRORS IN PREDICTING SPECIES RANGE SHIFTS
In the context of this report, "microcosm experiments" are
experiments involving a small-scale model of a larger scale
system. The "climate envelope approach" in the study of biotic
responses to climate change involves mapping the current
distribution of a species in the relevant climate-space, and upon
a change in the position of that climate-space, using the
previous mapping to predict shifts in the distribution of that
species. ... ... Davis et al (5 authors at 2 installations, UK)
report microcosm experiments on simple assemblages involving 3
fruit fly species to demonstrate how misleading the climate
envelope approach can be. The authors suggest that population
dispersal and population interactions, which are important
elements of population dynamics, must be included in predictions
of biotic responses to climate change, and in particular in
predictions of the effects of global warming on conservation,
medical considerations, and agricultural pest control. QY: Andrew
J. Davis
(Nature 19 Feb 98)
7. USE OF COULOMB EXPLOSION TO OBSERVE FEMTOSECOND REACTIONS
In general, a "Coulomb explosion" is any intense dispersion of
like-charged particles due to Coulomb repulsion. In physics, one
method of producing the phenomenon is to accelerate a molecule to
a high velocity, and then have it strike a solid, which results
in stripping of bonding-electrons in the molecule due to
repulsive collisions with electrons in the solid, and subsequent
explosive repulsive dispersal of like-charged atomic fragments.
In this report, Coulomb explosion in the first femtosecond time-
frame of an initiated chemical reaction was produced by an
intense laser pulse that ionized particles, the resulting
repulsive explosion stopping the reaction instantaneously, with
the masses of the fragments being subsequently measured, and the
measurements used to identify reaction entities and intermed-
iates. The hydrogen-bonded 7-azaindole dimer is a model often
used to investigate proton transfer between DNA base pairs.
... ... Welford et al (Pennsylvania State University, US) report
the above Coulomb explosion method to arrest chemical reactions
on a femtosecond time scale, with a specific study of the
hydrogen-bonded 7-azaindole dimer. Chemists apparently consider
this new technique an important addition to the tools available
for detection of femtosecond processes and the analysis of
chemical reaction intermediates. QY: A. Welford Castleman Jr.,
Pennsylvania State Univ. 814-863-8461 (Chem. Phys. Lett. in
press) (Chem. & Eng. News 23 Feb 98)
(continued in Part 2)
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SCIENCE-WEEK - Part 2/3
A Free Weekly Digest of the News of Science
March 6, 1998
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Contents of Part 2:
8. Using DNA as a Template for Assembling a Wire Connection
9. A Study of Protein Hydration in the Gaseous Phase
10. A Mathematical Model of Dynamical Principles in Bio-Processes
11. A Unified View of Polymer Nearest-Neighbor Thermodynamics
12. Single Secretory Vesicles Probed by Capillary Electrophoresis
13. Genetic Interference by Double-Stranded RNA in C. Elegans
14. Targeted Mutagenesis by Peptide Nucleic Acids
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8. USING DNA AS A TEMPLATE FOR ASSEMBLING A WIRE CONNECTION In
the context of this report, the term "hybridization" refers to
complementary pairing of molecular entities. ... ... Braun et al
(4 authors at Technion-Israel Institute of Technology, IL) report
a two-step procedure that may allow the application of DNA to the
construction of functional electronic circuits, the method
involving hybridization of the DNA molecule with surface-bound
oligonucleotides, then stretching the DNA molecule between 2 gold
electrodes, then using the DNA molecule as a template for the
vectorial growth of a 12-micron long, 100 nanometer wide
conductive silver wire. The authors suggest the experiment
confirms that the remarkable recognition capabilities of DNA can
be exploited for the targeted attachment of functional wires in
functional nanoscale electronic devices.
QY: Erez Braun (Nature 19 Feb 98)
Related Background:
A NEW METHOD FOR SYNTHESIS OF NANOWIRES
Nanowires (and nanotubes) are nanoscale [of the order of 10^(-9)
meters] structures that are effectively one-dimensional, and such
structures have great potential importance in many applications
ranging from probe microscopy to nanoelectronics. There are a
number of methods of producing one-dimensional nanoscale
structures, but so far none of them has allowed enough control of
structure parameters to be satisfactory. Vapor-liquid-solid
growth is a method of forming crystalline wire-like structures
with a liquid metal cluster or catalyst acting as the energetic-
ally favored site for absorption of gas-phase reactants. What
happens is that the cluster supersaturates and grows a one-
dimensional structure of the material, and the lower diameter
limit of the grown one-dimensional structure is apparently the
diameter of the liquid metal cluster starting locus. In the
context of this report, the term "laser ablation cluster
formation" refers to the use of a laser to reduce (ablate) a
cluster to nanoscale dimensions. ... ... Morales and Lieber
(Harvard Univ., US) report a method combining laser ablation
cluster formation and vapor-liquid-solid growth to synthesize
semiconductor nanowires, the laser ablation used to prepare
catalyst clusters that define the size of wires produced. The
authors suggest that well-established phase diagrams can be used
to predict catalyst materials and growth conditions for the
controlled preparation of crystalline nanowires of many different
materials. QY: Charles M. Lieber
(Science 9 Jan 98)
9. A STUDY OF PROTEIN HYDRATION IN THE GASEOUS PHASE
The technique of electrospray mass spectrometry involves the
dispersion of highly charged droplets from a capillary in a
strong electric field at atmospheric pressure. Heat or dry gas is
applied to the droplets to help evaporate the solvent, and
multiply charged ions expelled from the droplets during the
evaporation process are then mass analyzed. In this report, the
technique was varied by directing dehydrated ions (proteins) from
an electrospray source into a water-containing drift tube, and
then determining the partial rehydration of the gaseous ions by
mass analysis. ... ... Jarrold et al (Northwestern University,
US) report the use of electrospray mass spectrometry to study the
hydration of proteins in the gas phase. The authors suggest that
using their technique, they can effectively add one water
molecule at a time, get thermodynamic information for the
addition of individual water molecules, and examine how addition
of the water affects the conformation of the protein. QY: Martin
F. Jarrold, Northwestern Univ., Dept. of Chemistry 847-491-2968
(J. Am. Chem. Soc. 120:1327 1998)
10. A MATHEMATICAL MODEL OF DYNAMICAL PRINCIPLES IN BIO-PROCESSES
Charge transfer is classically a weak bond involving a coupling
between delocalized pi-electrons and a cation species, and in the
general sense, particularly in suitably composed polymers, the
term is used to describe an actual translocation of charge (an
electron transfer or an effective "hole" transfer) resulting from
classical charge-transfer coupling. In physics, an "exciton" is
an excited state of an insulator or semiconductor that allows
energy to be transported without transport of electric charge,
the result the existence of a virtual particle consisting of an
electron and a hole in a bound state. ... ... Schlag et al (4
authors at 3 installations, DE TW US) present a mathematical
analysis of certain dynamical principles in biological systems,
and in particular use the model to explain the effectiveness of
charge transfer (electron transfer reactions) in biological
systems. The model involves a system of first order linear
differential equations (with associated rate constant parameters)
to represent the kinetics of an electron transfer process, with a
special case solution for identical intermediates that allows
application of the theory of molecular excitons and determination
of the conditions under which the sequential transfer process is
most effective. QY: P.M. Rentzepis
(Proc. Natl. Acad. Sci. US 17 Feb 98)
11. A UNIFIED VIEW OF POLYMER NEAREST-NEIGHBOR THERMODYNAMICS
In the context of this report, the term "oligonucleotide dumb-
bell" refers to a structural type, and the term "oligonucleotide
duplex" refers to a double-stranded oligonucleotide. The term
"nearest-neighbor thermodynamics" refers to a thermodynamic model
of nucleic acids that assumes the stability of a given base pair
depends on the identity and orientation of neighboring base
pairs. ... ... J. SantaLucia Jr. (Wayne State University, US)
reports a unified approach to polymer, dumbbell, and oligonucleo-
tide nearest-neighbor thermodynamics, with DNA nearest-neighbor
free energy parameters from 7 different laboratories presented in
the same format to enable detailed comparisons. The 7 studies
involve data from natural polymers, synthetic polymers, oligo-
nucleotide dumbbells, and oligonucleotide duplexes originally
presented with different methods of analysis, different salt
concentrations, and different nearest-neighbor thermodynamic
formats. The author suggests that six of the studies are in
remarkable agreement with one another, with explanations
available for the remaining discrepancies, and that a single set
of nearest-neighbor parameters, derived from 108 oligonucleotide
duplexes, adequately describes polymer and oligomer thermodyn-
amics. QY: John SantaLucia Jr.
(Proc. Natl. Acad. Sci. US 17 Feb 98)
12. SINGLE SECRETORY VESICLES PROBED BY CAPILLARY ELECTROPHORESIS
Gastropods mollusks are a large class of mollusks, including
slugs and snails, and characterized by a well-developed head with
tentacles and eyes, a single shell, and a large flat foot.
Aplysia californica is a gastropod mollusk of rather large size.
The term "secretory vesicles" refers to intracellular spheroids
with sizes ranging from 30 nanometers to 2 microns in diameter
and bounded by a bimolecular layer membrane, various vesicles
containing various chemical messenger substances, especially in
the nervous system, where they contain neurotransmitter
substances. The vesicles investigated in this report had an
average diameter of 1 micron, and were from the reproductive
system of the animal. Electrophoresis is an electrochemical
process in which colloidal particles or macromolecules with a net
electric charge migrate in a solution under the influence of an
electric field, and the term "capillary electrophoresis" is a
technique for the electrophoretic sequestering of small particles
in the lumen of water-filled glass capillaries for chemical and
physical analysis. In this report the glass capillaries had an
inner diameter of 25 microns. ... ... Chiu et al (9 authors at 3
installations, US SE) report a method for chemical analysis of
individual secretory vesicles obtained from a gland of Aplysia
californica, the procedure involving a combination of capillary
electrophoresis separation and laser-induced fluorescence
detection of chemical entities. The results indicate distinct
variations in the contents of single vesicles, and the authors
suggest the method is the beginning of an era in which the
information contained in a single vesicle can be probed and
deciphered. QY: Richard N. Zare, Stanford Univ., Dept. of
Chemistry 415-723-2501 (Science 20 Feb 98)
13. GENETIC INTERFERENCE BY DOUBLE-STRANDED RNA IN C. ELEGANS
The term "gene-interfering RNA" refers to RNA that has been
experimentally introduced into certain biological systems to
interfere with the function of an endogenous gene. The effects
have been interpreted as involving a simple hybridization between
the injected RNA and endogenous messenger RNA transcripts, with
"messenger" RNA the RNA produced by transcribing the DNA code
into RNA code. Caenorhabditis elegans is a hermaphroditic,
microscopic, free-living soil nematode (roundworm) that feeds
mainly on bacteria, and it has become a powerful research model
in the study of animal development and behavior because it is
amenable to genetic analysis, has a relatively small number of
cells, and a large number of genes required for its normal
development and behavior have been identified by generating
mutations. "Germline cells" (as opposed to somatic cells) are
cells destined to become egg cells or sperm. ... ... Fire et al
(6 authors at 3 installations, US), investigating the require-
ments for structure and delivery of injected gene-interfering
RNA, report that double-stranded RNA was substantially more
effective at producing interference than either strand individ-
ually, and that after injection into adult animals (C. elegans),
purified single strands had at most a modest effect, whereas
double-stranded mixtures caused potent and specific interference.
Since only a few molecules were required per infected cell, the
authors suggest there could be a catalytic or amplification
component in the interference process, and that the ability of
double-stranded RNA to work at a distance from the site of
injection, and in particular to move into both germline and
muscle cells, suggests there is an effective RNA-transport
mechanism in C. elegans. QY: Andrew Fire
(Nature 19 Feb 98)
14. TARGETED MUTAGENESIS BY 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, and such molecules are known to bind to
single-stranded DNA. 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)
(continued in Part 3)
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
SCIENCE-WEEK - Part 3/3
A Free Weekly Digest of the News of Science
March 6, 1998
Contents of Part 3:
15. Collapse of Plasmid DNA into Stable Virus-Like Particles
16. Bcl-2 Prevents Apoptosis by Proton Flux Regulation
17. Use of Caged Peptides to Reveal Cell Signaling Pathways
18. Malaria: Genetics of Host-Parasite Coevolution
19. On Cellular Responses to Interferons and Other Cytokines
20. Farnesyl Transferase Inhibitors as Anti-Tumor Agents
----------------------------------------------------------------
15. COLLAPSE OF PLASMID DNA INTO STABLE VIRUS-LIKE PARTICLES
In biology, a "plasmid" is a small, usually circular, extra-
chromosomal genetic element (usually a single molecule of DNA)
that replicates independently of nuclear DNA. Plasmids occur in
bacteria, yeast, and certain more complex cell types. Because of
their accessibility, and the fact that plasmid DNA can be
integrated into the primary genome of the cell, they have been
used as cloning "vectors", i.e., a means to introduce exogenous
DNA into a genome. In general, a "detergent" is any linear
molecule containing a polar group attached to a long-chain fatty
acid moiety, the molecule exhibiting both hydrophobic and
hydrophilic interactions and tending to self-organize in
solutions. The primary lipid chemical constituents of cell
membranes are all chemically related to detergents. A "mono-
disperse" system of small particles in a liquid suspension is a
system in which the suspended particles have identical size,
shape, and interactions. ... ... Blessing et al (3 authors at
University of Strasbourg, FR) report a method of combining
properties of cationic lipids and cationic detergents with
plasmid DNA to produce virus-like particles with a stable core,
the procedure involving individual anionic plasmid molecules
cooperatively collapsed with a tailored cationic cysteine-based
detergent subsequently dimerized into a cystine-lipid. The
population of 23 nanometer spherical particles is monodisperse
and stable in physiological conditions over days, and with a
negative surface potential. The authors suggest the properties of
these particles should ensure good tissue dissemination and
escape from the bloodstream after intravenous injection, and that
the most promising future for these small negatively charged DNA-
containing particles will be in vivo artificial gene delivery
without the immunological problems raised by viruses.
QY: Jean-Paul Behr
(Proc. Natl. Acad. Sci. US 17 Feb 98)
16. BCL-2 PREVENTS APOPTOSIS BY PROTON FLUX REGULATION
Mitochondria are double-membrane enclosed organelles of cells
that are involved with several important biochemical pathways,
including electron transport and oxidative metabolism, and across
the membrane of the mitochondrion there exists a potential
difference apparently due primarily to a concentration gradient
of hydrogen ions. Biological cells are programmed to self-
destruct under certain condition, for example, when there is a
serious genome replication error, and the self-destruct sequence
is called "apoptosis". Cancer cells, which are derived from
normal cells whose genomes have undergone certain specific
mutations, require for their proliferation the activation in
their genome of genes that prevent apoptosis. The gene
has been identified as such a gene, and is called a "proto-
oncogene". This gene expresses the protein Bcl-2, and this
protein has been shown to prevent the loss of the mitochondrial
membrane potential, one of the events involved in apoptosis.
... ... Shimizu et al (8 authors at 2 installations, JP FR)
report that the protein Bcl-2 prevents both the loss of the
mitochondrial membrane potential (depolarization) and the
permeability transition induced by various reagents (e.g.,
Ca(sup2+), H(sub2)O(sub2), and tert-butyl hydroperoxide). The
authors suggest their results indicate Bcl-2 maintains the
mitochondrial membrane potential by enhancing H(sup+) efflux in
the presence of stimuli that induce depolarization.
QY: Yoshihide Tsujimoto
(Proc. Natl. Acad. Sci. US 17 Feb 98)
-------------------
Related Background:
APOPTOSIS: RELEASE OF CYTOCHROME C IS NOT SUFFICIENT
Transfection is the uptake of exogenous (foreign) DNA fragments
in solution directly into animals cells in laboratory culture,
and is one method of introducing foreign genes into cells. Bcl-2
is a protein that interferes with the activation of caspases by
preventing the release of cytochrome c, and Bax is a homolog of
Bcl-2 that promotes apoptosis. The term "membrane blebbing"
refers to the macroscopic blistering of the surfaces of cells
when they die under certain conditions. ... ... Rosse et al (8
authors at 2 installations, CH AT) report that in cells
transiently transfected with the gene , the protein Bax
localizes to mitochondria and induces the release of cytochrome
c, activation of caspase-3, membrane blebbing, nuclear fragment-
ation, and cell death. It was also found that cells overexpress-
ing both proteins Bcl-2 and Bax show no signs of caspase activ-
ation and survive with significant amounts of cytochrome c in the
cytoplasm. The authors suggest their findings indicate Bcl-2 can
interfere with Bax-induced apoptosis downstream and independent
of cytochrome c release.
QY: Christoph Borner
(Nature 29 Jan 98)
17. USE OF CAGED PEPTIDES TO REVEAL CELL SIGNALING PATHWAYS
In the context of this report, a "caged peptide" is a peptide
that has essentially been protected from interactions by an
attached photolabile moiety, the protection removed suddenly when
the photolabile moiety is activated by light of suitable wave-
length. A kinase is an enzyme that catalyzes the transfer of a
phosphate group from one compound to another. Calmodulin is a
Ca(2+) binding protein that mediates many of the regulatory
effects of calcium ions in eukaryotic cells (cells with
organelles such as nuclei). Myosin is the predominant structural
protein found in muscle and other contractile structures, and
myosin light chain kinase is a calcium-calmodulin dependent
enzyme that phosphorylates a low-molecular-weight moiety of
myosin and is involved in the contraction of smooth muscle.
Eosinophils are white blood cells (leukocytes) that stain readily
with eosin dyes. ... ... Walker et al (8 authors at 2 installat-
ions, US) report the development of caged peptides whose
influence on specific proteins can be suddenly and uniformly
changed by near-UV light, and report results from the use of two
of these peptides in vitro and in vivo to alter the activities of
isolated enzymes and cellular functions known to depend on
calcium-calmodulin and myosin light chain kinase. The caged
peptides were injected into motile eosinophils, and when exposed
to light promptly blocked cell locomotion in a similar manner.
The authors suggest this methodology provides a powerful means
for assessing the role of calcium-calmodulin and myosin light
chain kinase and other proteins in a wide range of complex
functions in intact living cells.
QY: Jeffrey W. Walker
(Proc. Natl. Acad. Sci. US 17 Feb 98)
18. MALARIA: GENETICS OF HOST-PARASITE COEVOLUTION
Malaria, an infectious disease caused by a parasitic protozoan
transmitted by a mosquito bite, blood transfusion, or the use of
a common syringe by drug addicts, kills one or two million people
each year. There are actually 4 types of protozoan parasites that
cause the disease, with Plasmodium falciparum the most dangerous.
An antigen is any chemical moiety that provokes an immune
response in vertebrates, in particular by binding to an antibody,
and the term "epitope" refers to the region of an antigen
molecule responsible for its specificity in an antigen-antibody
interaction: the epitope is recognized by the antigen-binding
site of a specific antibody molecule. Cytotoxic T-cells are cells
of the vertebrate immune system that kill foreign cells by
production of certain proteins. In cell biology, the term "down-
regulation" refers to a gradual desensitization of cell surface
receptors that occurs upon repeated exposure to their specific
ligands. The term "host-parasite coevolution" refers to an
interdependent simultaneous evolution of a parasite species and
its host species. ... ... Hill et al (10 authors at 3 install-
ations, UK GM) report a study of the variants of an antigenic
epitope of Plasmodium falciparum that induces a cytotoxic T-cell
response. It was found that in African children with malaria, the
extant epitope variants are influenced by the presence of a human
leukocyte antigen type that restricts the immune response to this
epitope. The authors suggest that the distribution of parasite
variants may be further influenced by the ability of cohabiting
parasite strains to facilitate each other's survival by down-
regulating cellular immune responses using altered peptide ligand
antagonism, and that combined genetic, immunological, and
mathematical analyses of further such examples from natural
populations should provide a molecular understanding of the
mechanisms driving host-parasite coevolution.
QY: Adrian V.S. Hill
(Science 20 Feb 98)
19. ON CELLULAR RESPONSES TO INTERFERONS AND OTHER CYTOKINES
Interferons are a class of small glycoproteins (mol. wt. 26K to
38K) that interfere with the RNA synthesis necessary for the
replication of RNA viruses, a group of viruses in which the core
of the virus consists of RNA rather than DNA. Interferons also
have many non-antiviral actions involving many cell functions,
and they belong to the general class of cytokines, which are a
variety of low-molecular weight proteins with hormone-like prop-
erties secreted by many cell types. JAK enzymes (Janus kinases)
are receptor-associated kinases interacting with various cytokine
ligands, particularly interferon, and also interacting with
moieties and processes in the interior of the cell. The term
"STATs" refers to signal transducers and activators of trans-
cription, and together with the Janus kinases they mediate the
signaling mechanism known as the JAK-STAT pathway, which is known
to provoke the transcription of certain regulated genes.
... ... R. Ransohoff (Cleveland Clinic Foundation, US), in a
short review of the cellular responses to interferon and other
cytokines, and in particular the involvement of the JAK-STAT
pathway, notes that in the past 5 years more than 1000 research
papers have been published concerning the newly-discovered JAK-
STAT pathway, and that the discovery was actually a serendipitous
outcome of research on interferon. The author suggests that
future applications of research on the JAK-STAT pathway will
concern the problem of cellular resistance to interferon, a
problem prevalent in treating neoplastic, infectious, and
inflammatory diseases.
QY: Richard M. Ransohoff, Cleveland Clinic Foundation, Cleveland,
OH 44195 US (New England J. Med. 26 Feb 98)
20. FARNESYL TRANSFERASE INHIBITORS AS ANTI-TUMOR AGENTS
Farnesol is a conjugated chain alcohol, and farnesyl pyrophos-
phate is an intermediate in the biosynthesis of squalene, with
the enzyme farnesyl transferase involved in this synthesis.
Squalene, in turn, is ultimately converted to cholesterol and
various steroids of paramount importance in the functions of
cells. 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 and the mechanical processes involved in cell
division. Especially in the last case, both the assembly and
disassembly of microtubules are an essential aspect of proper
cell function. Members of the family of genes are mutated
in approximately 30% of human cancers, and the Ras proteins have
a farnesyl moiety that results in the protein becoming membrane-
associated. The taxanes (diterpenes composed of 3 pentadecene
rings) are a chemical group some of which are cytotoxic drugs
(e.g., taxol, a diterpene amide from the yew tree) that prevent
microtubule disassembly, acting as mitotic inhibitors, and are as
a result antineoplastic (antitumor) agents. In general, the term
"wild-type" refers to the natural or unmutated variant of an
organism or genetic character. ... ... Moasser et al (8 authors
at 2 installations, US) report that when farnesyl transferase
inhibitors are combined with certain cytotoxic antineoplastic
drugs, the effects on tumor cells are additive, no interference
is noted, and farnesyl transferase inhibitors and agents that
prevent microtubule depolymerization (e.g., taxol or epothilones)
act synergistically to inhibit cell growth. The authors suggest
that farnesylated protein may be one of the regulators of
mitosis, and that farnesyl transferase inhibitors may be useful
agents for the treatment of tumors with wild-type genes
that are sensitive to taxanes. QY: Neal Rosen
(Proc. Natl. Acad. Sci. US 17 Feb 98)
---------------------------------------------
BOOK NOTES:
A.P. Fairall (ed.): LARGE-SCALE STRUCTURES IN THE UNIVERSE
Wiley, 1998, 200p, US39.95
Distribution of the galaxies, formation and structure of the
universe, redshifts, methods of mapping the cosmos, galaxy
formation, n-body simulations, descriptions of planned large-
scale projects.
A.P. Guimaraes: MAGNETISM AND MAGNETIC RESONANCE IN SOLIDS
Wiley, 1998, 304p, US69.95
A reference with a focus on research aspects in physics,
medicine, materials science, and engineering. Nuclear magnetic
resonance, hyperfine interactions in condensed matter,
microscopic study of magnetism in matter.
John B. Hudson: SURFACE SCIENCE
An Introduction
Wiley, 1998, 336p, US44.95
Structure, thermodynamics, and mobility of clean surfaces;
interaction of gas molecules with solid surfaces; techniques
involving energetic particle interactions; crystal nucleation and
growth.
Steven M. Kaplan:
ENGLISH-SPANISH, SPANISH-ENGLISH CHEMICAL DICTIONARY
Wiley, 1998, 544P, US39.95
40,000 essential terms and phrases found in chemical literature.
Robert E. Maizell: HOW TO FIND CHEMICAL INFORMATION
A Guide for Practicing Chemists, Educators, and Students
3rd Edition
Wiley, 1998, 523p, US64.95
This edition is an update and rewrite. The Internet as a major
research tool, CDROM sources, electronic databases, scientific
journals, commercial and trade publications.
Francis M. Mirabella:
MODERN TECHNIQUES IN APPLIED MOLECULAR SPECTROSCOPY
Wiley, 1998, 432p, US74.95
Characteristics, principles, and applications of various
molecular spectroscopy techniques, methods of selection, sample
preparation, troubleshooting, data handling.
Jeremy Narby: THE COSMIC SERPENT
DNA and the Origin of Knowledge
Tarcher, 1998, 239p, US21.95
This is journalistic science-writing at its worst. The author's
thesis is that since the motif of intertwined spiral strands,
especially intertwined spiral snakes, appears in a variety of
designs and artistic works executed by ancient and currently
primitive people, primitive people have been aware of DNA for
thousands of years and these motifs are metaphors for the double
helix of DNA, that current primitive people via hallucinations
somehow gain specific new factual knowledge transferred through
DNA, the entire story discovered by the author "during ten years
of intense study in the Amazonian rainforest and in the libraries
of Europe." Unfortunately, the book is being touted by some
anthropologists as a work to be taken seriously.
Eugene P. Odum: ECOLOGY
A Bridge Between Science and Society
Sinauer, 1997, 330p, US24.95
An undergraduate text. Basic ecological systems and principles,
Earth as a life-support environment, theories of ecological
hierarchy, ecosystem models, documentation of concepts, pioneers
of ecological thought. The author is an ecologist.
W.P. Schleich: QUANTUM OPTICS IN PHASE SPACE
Wiley, 1998, 282p, US70
An introductory text in the theoretical aspects of quantum
optics. Quantization of the radiation field, phase space
distribution functions, the density operator, the quantum
mechanical beam splitter, semiclassical quantum mechanics,
interaction between atoms and the quantized light field, quantum
theory of damping.
N. Sleep and K. Fujita: PRINCIPLES OF GEOPHYSICS
Blackwell, 1997, 586p, US69.95
An undergraduate/graduate text. History of geophysics and its
methodologies, gross structure of the Earth, plate tectonics,
geological time, methods of dating events, gravity, heat flow,
magnetic methods, paleomagnetic methods, equations of motion,
amplitudes, surface waves, free oscillations of the Earth,
mathematical treatment of paleontology and geodynamics. The
authors are geophysicists.
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