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ScienceWeek
SCIENCE-WEEK - February 15, 2002 - Vol. 6 Number 7
An Email Research Digest Published Weekly Since 1997
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-- Niels Bohr (1885-1962)
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Section 1
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Contents of this Issue (Full reports in Section 2):
Basic Sciences
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1. Biophysics: Packing of DNA in a Virus
2. The Enzyme Lipoxygenase
3. On Exact Solutions for Many-Body Systems
4. Mystery of Galaxy Formation
5. Helicate Chemistry
6. Nature of Chemical Bonds
7. Fuel Loads and Bird Migration
8. On Repression of Transcription
9. The Human Genome and Human Life
10. Metaphors and the Language of DNA
11. On Neural Stem Cells
12. On the Dendrites of Nerve Cells
Praxis
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13. Self-Assembly and Mineralization of Nanofibers
14. On Metal-Containing Polymers
15. Long-Distance Quantum Communication
16. A Computing Machine Made of Biomolecules
17. Packing of Spherical Granular Material
18. Two-Level Josephson-Junction Systems in Quantum Computing
19. Epstein-Barr Virus and Multiple Sclerosis
20. Risk of Attempted Suicide Throughout the Lifespan
21. Very-Low-Birth-Weight Infants 20 Years Later
22. Aquaculture and Aquatic Invasive Species
23. Analysis of the UK Creutzfeldt-Jakob Disease Epidemic
24. On University-Industry Connections
Miscellany
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25. Postdoctoral Fellowship Profile:
Laboratory of Wolf-Dietrich Heyer at Univ. of California Davis
26. In Focus: On Studying Fossils (Ian Tattersall)
27. New Books
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Section 2
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1. BIOPHYSICS: ON THE PACKING OF DNA IN A VIRUS
Bacteriophages (bacterial viruses; phages) are the largest
virus group, with approximately 4000 different types isolated.
They are viruses that infect bacteria only, usually no more than
one or a few particular species of bacteria for each type of
phage, and they occur throughout the bacterial world and in all
bacterial habitats, even volcanic hot springs. Their dimensions
are on the order of 50 to 200 nanometers, depending on phage
type.
... ... D.E. Smith et al (University of California Berkeley, US)
discuss the packing of DNA in a bacteriophage, the authors making
the following points:
1) As part of the viral infection cycle, viruses must
package their newly replicated genomes for delivery to other host
cells. Bacteriophage phi-29 packages its 6.6-micron long double-
stranded DNA into a 42 x 54 nanometer capsid by means of a portal
complex that hydrolyzes ATP. This process is remarkable because
entropic, electrostatic, and bending energies of the DNA must be
overcome to package the DNA to near-crystalline density.
2) The authors report they use optical tweezers to pull on
single DNA molecules as they are packaged, thus demonstrating
that the portal complex is a force-generating motor. This motor
can work against loads of up to 57 piconewtons on average, making
it one of the strongest molecular motors reported to date.
Movements of over 5 microns are observed, indicating high
processivity. Pauses and slips also occur, particularly at higher
forces.
3) The authors establish the force-velocity relationship of
the motor and find that the rate-limiting step of the motor's
cycle is force dependent even at low loads. Notably, the
packaging rate decreases as the prohead is filled, indicating
that an internal force builds up to approximately 50 piconewtons
owing to DNA confinement. The authors suggest their data indicate
that this force may be available for initiating the ejection of
the DNA from the capsid during infection of the bacterium.
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Nature 2001 413:748
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SCIENCE-WEEK 15 Feb 2002 www.scienceweek.com
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Related Background:
PHAGE DISRUPTION OF BACTERIAL WALLS
... Bacteriophages were discovered independently by Frederick W
Twort (1877-1950) in 1915 and Felix d'Herelle (1873-1949) in
1917. It was D'Herelle who coined the term "bacteriophage"
(bacteria-eater) to describe the bacteriocidal action of the
virus. Neither discovery involved direct observation of
bacteriophages; instead, clear spots in bacterial culture films
were recognized (particularly by d'Herelle) as indicating the
presence of an organism killing bacteria.
In general, phages destroy or genetically modify bacteria,
with destruction caused by disintegration produced by disruption
of cell walls (lysis) of infected bacteria. Alternatively,
surviving bacteria can become phage-infected without lysis and
simply acquire new properties as a consequence of incorporation
of phage DNA into the bacterial genome.
Phages consist essentially of nucleic acid (DNA or RNA), a
protein coat (capsid), and, in some cases, lipid. Four structural
groups of phages have been categorized: a) isometric particles
with cubic symmetry; b) helical filaments or rods; c) tailed
phages with cubic capsids (the "heads") and helical tails; d)
pleomorphic particles without definite structure. When capsids
with cubic symmetry are present, these are icosahedra or related
bodies.
Phages typically adsorb to specific receptors on the
bacterial cell wall, but also to other parts of bacteria (e.g.,
to flagella). Most phages have apparent fixation organelles such
as fibers, spikes, or adsorption proteins. Tailed phages have
molecular devices for injecting their nucleic acid into the
bacterial host cell. A typical lysis cycle (lytic cycle) involves
a latent period of 20 to 40 minutes after phage infection of a
bacterium, the latent period ending in the release of 50 to 200
new phages, with the release accomplished by lysis (bursting) of
the host cell.
Phage morphogenesis, always inside a host cell, is a complex
and highly ordered process which may involve separate pathways
for different phage constituents. In tailed and most cubic
phages, phage nucleic acid enters capsids after the capsids are
formed. In other types of phages, the capsid condenses around the
phage nucleic acid. In still other types of phages, the capsid
and nucleic acid assemble at the host-cell periphery as the virus
particle is extruded.
It is believed that bacteriophages came into existence
perhaps earlier than 3 billion years ago, apparently before the
separation of bacteria into two kingdoms (eubacteria and
archaebacteria), with tailed phages probably originating first.
Phage viruses such as the T4 phage, with its jointed "legs" and
injection apparatus that moves its genome into the interior of a
bacterial cell, are among the most fascinating replicating
supramolecular systems known to biologists.
... ... Graham F. Hatfull (University of Pittsburgh, US)
discusses current research on phage lysis of bacteria. Lytic
bacteriophages face a conundrum: Once the invading phage has
replicated inside the bacterial host cell, how can its progeny
escape from the bacterium to infect other cells? Most bacteria
are surrounded by a tough wall composed of a cross-linked
peptide-sugar (peptidoglycan) matrix that protects the bacterial
cell membrane and that helps to maintain the shape of the
bacterium. Building and maintaining this peptidoglycan matrix is
problematic for bacteria because the wall must be strong enough
to withstand the osmotic pressure from within, yet flexible
enough to be constantly remodeled as the bacterium divides and
grows. T.G. Bernhardt et al (2001) have demonstrated that some
bacteriophages have adopted strategies to block bacterial enzymes
in the peptidoglycan synthesis pathway. It is already known that
other phages produce their own enzymes to smash through bacterial
cell walls and permeabilize bacterial cell membranes. Lysis of
bacterial walls needs to be closely coordinated with virus
replication and the assembly of viral progeny, since premature
rupture of the bacterial membrane and wall would kill forming
phage progeny by stopping the assembly process.
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Science 2001 292:2263,2326
SCIENCE-WEEK 2001 10 Aug
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SCIENCE-WEEK 15 Feb 2002 www.scienceweek.com
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2. ON THE ENZYME LIPOXYGENASE
E. Skrzypczak-Jankun et al (University of Toledo, US) discuss the
enzyme lipoxygenase, the authors making the following points:
1) Polyunsaturated fatty acid metabolism is governed by two
enzymes, cyclooxygenase and lipoxygenase, and together these
enzymes are responsible for the inauguration of the biosynthesis
of a host of metabolites known collectively as "eicosanoids". The
discovery that these compounds play pivotal roles in diseases
that include an inflammatory component has produced a substantial
research effort to elucidate the structure and mechanism of
action of these key biosynthetic enzymes.
2) Structure/function studies of cyclooxygenase have
culminated in the discovery of numerous inhibitors with
therapeutic potential, the non-steroidal antiinflammatory drugs
(called "COX inhibitors"). Parallel investigations into the
structure of lipoxygenase and its complexes with small molecules,
e.g., substrate, product, and inhibitors, for the generation of
therapeutically useful compounds have not reached the same level
of development.
3) Lipoxygenase catalysis depends on the participation of a
unique non-heme iron cofactor. The enzyme activates the substrate
polyunsaturated fatty acid toward combination with molecular
oxygen by a hydrogen atom abstraction reaction. The results of
kinetic isotope effect experiments implicate a tunneling
mechanism for this key step in the catalyzed reaction, and how
the enzyme perpetrates the transformation in this way is
currently of considerable fundamental interest in chemistry.
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J. Am. Chem. Soc. 2001 123:10814
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3. ON EXACT SOLUTIONS FOR MANY-BODY SYSTEMS
Michel Heritier (Orsay Science Center, FR) discusses many-body
systems. During the past 40 years, understanding quantum systems
involving many particles has been one of the main goals of
theoretical physics. The focus of such research is not to work
out the laws of interactions between particles, but to assume
that these interactions are already known and to calculate their
effects on a system of (n) particles. A system where (n) is large
constitutes the so-called "many-body problem", and such a system
can exhibit rich behavior, including phase transitions,
superconductivity, and Bose-Einstein condensation. The impact of
exactly solvable theoretical models on research into these
systems is undeniable, but with few exceptions, previous exact
solutions have applied only to 1-dimensional systems. A wide
range of many-body systems has been studied, with varying numbers
of particles. For example, systems of nuclei, with (n) equal to
approximately 100 nucleons, are important in nuclear physics, and
atomic and molecular physics deal with systems involving
approximately 100 electrons, whereas mesoscopic systems, with (n)
in the range of 10^(2) to 10^(6) and macroscopic systems, with
(n) in the range of 10^(23), arise in condensed matter physics.
Real systems are usually extraordinarily complex and involve a
large set of parameters, most of which are irrelevant for
discussing the phenomena under investigation. So theoretical
physicists begin by defining a model -- i.e., an idealized system
much simpler than the real one, but retaining all the necessary
ingredients to discuss the physical properties of interest.
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Nature 2001 414:31
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4. ON THE MYSTERY OF GALAXY FORMATION
Marco Scodeggio (Institute of Cosmic Physics Milan, IT) discusses
galaxy formation, the author making the following points:
1) Most visible matter in the Universe is organized in
galaxies, but little is known about how and when galaxies formed
and how they evolved.
2) There are two basic models for galaxy formation: a) In
the monolithic collapse scenario, all galaxies were formed in a
single event through the gravitational collapse of a cloud of
primordial gas very early in the history of the Universe. b) In
the hierarchical merging scenario, galaxies are gradually
assembled through multiple mergers of smaller subgalactic units,
a process that continues from the early Universe to the current
epoch.
3) The differences between the two models extend to ideas
concerning galaxy evolution: a) In the monolithic collapse
scenario, galaxies of different morphological types (spirals and
ellipticals) are born as intrinsically different entities. b) In
the hierarchical merging scenario, galaxies end up as spirals or
ellipticals depending on the details of their merger history.
4) As a consequence, the first model (monolithic collapse)
predicts that the number of galaxies of a given type should be
approximately constant at all redshifts (i.e., throughout the
history of the Universe), whereas the second model (hierarchical
merging) predicts that the number of galaxies of a given type
should decrease with increasing redshift (i.e., decrease with
decreasing age of the Universe).
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Science 2001 294:537
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5. ON HELICATE CHEMISTRY
Markus Albrecht (University of Karlsruhe, DE) discusses
helicates, the author making the following points:
1) In chemistry or biochemistry, helicity is present in
various systems. For example, alpha-amylose is a macromolecule
with a helical structure that contains approximately 6 glucose
units per helical turn. DNA exists as a double helix in which the
two strands are connected by hydrogen bonding between
complementary bases. DNA stores and transmits our genetic make up
and therefore is essential for life. Peptides can adopt an alpha-
helical structure or form larger helical arrays, e.g., collagen
triple helices.
2) In artificial supramolecular architectures, helicity can
be introduced by conformational restrictions of macromolecules,
inter- or intramolecular hydrogen bonds, or coordination to metal
ions. A class of unnatural double- and triple-stranded helical
oligonuclear coordination compounds are formed in metal-directed
self-assembly processes. In 1987, J.M. Lehn introduced the term
"helicate" for metal complexes that contain one or more ligand
strands and two or more metal centers. The most common of such
coordination compounds are the double-stranded and triple-
stranded helicates, and the challenge of helicate chemistry is
not only to understand fundamental principles of recognition and
self-assembly processes, but also to search for new
supramolecular functional devices. Also, questions concerning the
influence of non-covalent interactions on supramolecular stereo-
and regiochemistry can be studied by using helicates as simple
model systems.
3) In general, the formation of helicates depends on the
nature of the metal and ligands and sometimes on additional
factors that can be introduced by appropriate templates or
reaction conditions. The chiral constraints that lead to the
formation of the helical structure are very often are embedded in
the preferred coordination geometry at the metal ion sites.
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Chem Revs. 2001 101:3457
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6. ON THE NATURE OF CHEMICAL BONDS
R.J. Gillespie (McMaster University, CA) discusses chemical
bonds, the author making the following points:
1) Conventional descriptions of bonds are based on two
limiting models -- the ionic model and the covalent model. The
ionic model assumes that molecules and crystals are composed of
spherical ions with integral charges held together by the
Coulombic attraction between these ions. However, there are no
purely ionic bonds even in crystals, since the ions are not truly
spherical and there is always a small amount of electron density
shared between the atoms. The covalent model assumes that atoms
are held together by the "sharing" of electron density.
2) According to G.N. Lewis (1875-1946), an electron pair is
shared if it is used to complete the valence shell of both bonded
atoms in a Lewis diagram. In terms of the electron density of a
molecule, the meaning of "sharing" is not so clear. It is
generally taken to mean that in a covalent bond electron density
is accumulated between the two atoms and it is the electrostatic
attraction between this density and the two nuclei that holds the
two atoms together. The only purely covalent bonds are those
between identical atoms in symmetrical molecules such as the C-C
bond in ethane and the Si-Si bond in disilane. Thus, the very
large majority of bonds have a character intermediate between
that of an ionic bond and that of a covalent bond. Such bonds are
usually described as "polar covalent", and almost all bonds may
be described as such.
3) However, this description leaves unanswered the question
of to what degree a bond is ionic or covalent. Bonds are often
said to have more or less "ionic character" and more or less
"covalent character". Unfortunately, these terms are vague and
cannot be rigorously defined. When a bond is said to have a large
ionic character, it is usually assumed that this means the bond
has a small covalent character, but this is not necessarily the
case. Ultimately all bonding, no matter how we describe it, is
the result of the attractive electrostatic force between the
electron density and the nuclei and the repulsive force between
the nuclei themselves. So the understanding and description of
chemical bonding ultimately depends on analyzing and
understanding the electron density distribution.
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J. Chem. Educ. 2001 78:1688
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SCIENCE-WEEK 15 Feb 2002 www.scienceweek.com
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Related Background:
IN FOCUS: ON CALCULATING THE CHEMICAL BOND
"Our understanding of why atoms combine together to form
molecules and why the most stable molecules satisfy the rules of
valence was unclear until the development of quantum mechanics.
Theoretical chemists now have available many computer packages
(prepared after huge efforts at writing software) that allow them
to obtain approximate solutions to the Schroedinger equation for
the electrons and to deduce the structure, stability, and other
properties of a molecule. It has, however, been very difficult to
obtain results that provide confident predictions for the
experimentalist, except for rather simple (few-electron)
molecules. Even today there are many calculations for which
theoretical chemists will happily call on the maximum computer
power available; so, it is necessary to explain why the
calculations are so difficult. The energy of a molecule is a
balance between the attractive forces between electrons and
nuclei and the repulsive forces acting between nuclei and between
electrons. Multiply-charged molecules, either positive or
negative, are rarely stable with respect to dissociation in the
gas phase because the repulsive forces win (in solution there are
other factors that affect the stability). Because nuclei are so
much heavier than electrons, one can obtain an energy for
electrons moving in a potential from fixed nuclei and then use
this to determine the nuclear motion; this is called the Born-
Oppenheimer approximation. It is the first of these tasks, that
of calculating the energy of the electrons, that is particularly
difficult, because the repulsion between the electrons is an
important part of the chemical bond energy and, for many
molecules, unless it is calculated with high accuracy, the
results are poor. The role of computers for chemical bond
calculations was mapped out in a landmark paper in _Nature_,
published in 1956 by Boys, Cook, Reeves, and Shavitt, under the
title 'Automatic fundamental calculations of molecular
structure'. They not only proposed a method that is still the
basis of many current calculations but also performed
calculations on what was then quite a complicated system, namely
the water molecule. They used the first University of Cambridge
computer, EDSAC, which carried out 1000 operations per second and
had a 1000-word store. A single calculation took 40 hours (how
did they keep it running?). Such a calculation today might take 4
seconds."
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John N. Murrell: Bonding and the Theory of Atoms and Molecules.
in: Nina Hall (ed.): _The New Chemistry_
(Cambridge University Press, Cambridge UK 2000, p.33
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SCIENCE-WEEK 2001 20 Apr
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7. ON FUEL LOADS AND BIRD MIGRATION
A. Kvist et al (Lund University, SE) discuss bird migration, the
authors making the following points:
1) Aerodynamic theory predicts that to support the weight of
the bird and to overcome the drag of the body and wings, the
mechanical power output the flight muscles generate increases
with fuel load. The available evidence indicates that the
aerodynamic models correctly describe the essential physical
processes involved.
2) Birds on migration alternate between consuming fuel
stores during flight and accumulating fuel stores during
stopovers. The optimal timing and length of flights and stopovers
for successful migration depend heavily on the extra metabolic
power input (fuel use) required to carry the fuel stores during
flight. The effect of large fuel loads on metabolic power input
has never been empirically determined.
3) The authors report they measured the total metabolic
power input of a long-distance migrant, the red knot (Calidris
canutus), flying for 6 to 10 hours in a wind tunnel. The authors
report that total metabolic power input increased with fuel load,
but proportionally less than the predicted mechanical power
output from the flight muscles. The authors suggest the most
likely explanation is that the efficiency with which metabolic
power input is converted into mechanical output by the flight
muscles increases with fuel load. This will influence current
models of bird flight and bird migration, and may also help to
explain why some shorebirds, despite the high metabolic power
input required to fly, routinely make nonstop flights of 4000
kilometers or longer.
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Nature 2001 413:730
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8. ON REPRESSION OF TRANSCRIPTION
A.J. Courey and S. Jia (University of California Los Angeles, US)
discuss transcriptional repression, the authors making the
following points:
1) Gene-specific repression of transcription plays a central
role in gene regulation. This is true for the spatial control of
gene activity in development, during which boundaries of gene
expression are often determined by the spatially restricted
localization or activity of transcriptional repressors. It is
also true for the control of gene expression by extracellular
signals, in which process genes are often maintained in an off
state by repressor proteins until signal transduction removes the
repression.
2) One of the most useful ways of categorizing repressors is
according to whether they mediate long-range or short-range
repression. In long-range repression, a repressor makes a
promotor resistant to the influence of all enhancers, even if
those enhancers are located thousands of base pairs from the
repressor binding site. This kind of repression is often called
"silencing", because an entire chromosome locus is inactivated.
In contrast, short-range repressors function in a less general
manner: rather than interfering with all transcription at a
locus, they block the function of nearby DNA-bound activators
while not interfering with more distantly bound activators.
3) Long-range repression may often involve the assembly of a
multi-protein complex called a "repressosome" that is analogous
in many ways to the "enhanceosomes" known to mediate activation.
Both long-range and short-range repression may involve the
recruitment of histone deacetylases to the template. It is
possible that interactions between repressors and the basal
machinery, as well as between repressors and activators, play
roles in long-range and short-range repression.
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Genes & Development 2001 15:2786
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9. ON THE HUMAN GENOME AND HUMAN LIFE
James D. Watson (Cold Spring Harbor Laboratory, US) discusses the
human genome, the author making the following points:
1) The author states: "That the human script would become
available within our lifetimes never passed through my mind or
that of Francis Crick when we found the double helix in 1953. At
that time, just learning how cells read the genetic instructions
within DNA seemed a tall order."
2) The author suggests that many unanticipated hypotheses
will emerge as the reading of the human DNA script extends beyond
those individuals who produced it to the much larger world of
interested biologists. Even the heartiest biologists, however,
will find themselves stretched if they take on too much. Most
triumphs of the near future will likely come from focusing on
human homologs of genes functionally understood in one or more
model organisms. Eventually, even more important dividends will
come from focusing on ourselves as human beings and making sense
of the often-seemingly intractable relations between nature and
nurture. There is much more to human life than interactions
between its DNA script and the RNA and protein "actors" that
carry out its instructions. The culturally-derived facts and
traditions that our brains pass onwards from one generation to
the next equally affect our lives. Thus, our genomes can never
accurately predict our futures. But we would be more than silly
if we did not use the information of our genomes to the fullest.
The human genetic script that we are now finalizing will be
regarded as the most important book ever to be read.
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Genome Research 2001 11:1803
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10. METAPHORS AND THE LANGUAGE OF DNA
John C. Avise (University of Georgia, US) discusses the language
of DNA. In the 20th century, "beads-on-a-string" was a prevailing
metaphor for how housekeeping genes (those that encode proteins)
were densely packed along each eukaryotic chromosome. Draft
sequences of the human genome have nailed the coffin shut on that
caricature. The coding "beads" make up less than 2 percent of our
DNA, and most are themselves subdivided into "beadlets" (exons)
interspersed with non-coding introns that comprise more than 95
percent of a typical transcription unit. Accordingly, some
researchers next visualized protein-coding genes as tiny
scattered oases in a genomic desert, implying that all else was a
wasteland. Fortunately, this view did not prevent the genomic
outback from being reconnoitered in the human genome project,
because the results were truly incredible. The intergenic
wilderness proved to be populated by a motley crew of intriguing
genetic characters: active promoters and regulators of gene
expression, comatose pseudogenes, descendants of immigrant DNAs
(perhaps horizontally transferred from microbes), vagabond
sequences, hordes of tandem short-repeats, and great armies of
repetitive elements -- some with hundreds of thousands of like-
uniformed members. Astonishingly, at least 50 percent of the
human sequence is derived from transposable elements that have
dispersed themselves across the genome either as mobile DNA or
via reverse-transcribed RNAs. Some of these smaller jumping genes
are free-loaders that hitch rides on the backs of larger roving
elements, like mites on fleas.
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Science 2001 294:86
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11. ON NEURAL STEM CELLS
Sally Temple (Albany Medical College, US) discuss neural stem
cells, the author making the following points:
1) The discovery of neural stem cells was rooted in
classical studies of *hematopoiesis and of invertebrate neural
development, which inspired examination of single neural
progenitor cells. In this context, the term "progenitor cell"
refers to all classes of immature proliferating cells. Neural
stem cells are a subtype of progenitor cells in the nervous
system that can self-renew and generate both neurons and
*neuroglial cells. The early studies led to the isolation of
stem-like cells from the embryonic mammalian central nervous
system and from the peripheral nervous system. Since then, stem
cells have been isolated from many regions of the embryonic
nervous system, suggesting their ubiquity.
2) After the discovery of neural stem cells in the embryo,
the first isolation of stem-like cells from adult brain began
another chapter of neuroscience. Adult neural stem cells have now
been found in the two principal adult neurogenic regions, the
*hippocampus and the *subventricular zone, and in some non-
neurogenic regions, including the spinal cord. These pioneering
studies provided a cellular mechanism for adult neurogenesis,
which was well-established in birds and is increasing recognized
in mammals, and this raised the possibility that the most
intractable of tissues, the central nervous system, might have
regenerative capabilities.
3) Markers that define central nervous system stem cells are
only now being developed. Thus, such cells are usually identified
retrospectively on the basis of their behavior after isolation.
In adherent in-vitro cultures, central nervous system stem cells
produce large clone aggregates containing neurons, glial cells,
and more stem cells. Central nervous system stem cells can also
be cultured as floating multicellular spherical aggregates.
Peripheral nervous system neural crest stem cells express the
low-affinity *neurotropin receptor p75, and grow as adherent
clonal aggregates containing peripheral neurons, glial cells,
*smooth muscle cells, and more stem cells.
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Nature 2001 414:112
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Notes:
... ... *hematopoiesis: (hemopoiesis) The process by which the
cells of the blood are formed.
... ... *neuroglial: In general, nerve cells in the central and
peripheral nervous systems of mammals (including humans) are
surrounded by satellite cells that play various roles in neural
function. In the central nervous system, these satellite cells
are called "neuroglial cells" (glial cells), and they constitute
approximately one-half of the volume of the human brain and
greatly outnumber neurons in the brain.
... ... *hippocampus: A region of the cerebral cortex in the
*medial part of the temporal lobe. In humans, among other
functions, the hippocampus is apparently involved in short-term
memory, and analysis of the neurological correlates of learning
behavior in animals indicates that the hippocampus is also
involved in memory in other species.
... ... *subventricular zone: Proliferating cells apparently
persist throughout adult life along the length of the lateral
wall of the internal brain fluid space known as the "lateral
ventricles". This germinal region, called the "subventricular
zone", generates new neurons destined for the part of the brain
receiving olfactory sensory information (olfactory bulb).
... ... *neurotropin: (neurotrophin) In general, neurons in the
central nervous system apparently depend for their survival on a
number of secreted substances called neurotrophins (neurotrophic
factors). These substances are polypeptides of 200 to 300 amino
acids, and at least 4 different neurotrophins have been
identified.
... ... *smooth muscle cells: Smooth muscle was originally
differentiated from striated muscle on the basis of microscopic
appearance, but there are important other differences both
functional and molecular. In general smooth muscle is
specialized for slow sustained contractions such as those
involved in the control of the diameters of blood vessels.
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12. ON THE DENDRITES OF NERVE CELLS
Y-N. Jan and L.Y. Jan (University of California San Francisco,
US) discuss neuron dendrites, the authors making the following
points:
1) When connections in the central nervous system are
effected, the axon of presynaptic neurons need to be properly
guided to make synapses with the correct targets, which are
usually the dendrites of the postsynaptic neurons. Dendrites are
not just passive participants in this process, and most likely,
synapse formation involves two-way communications between the
presynaptic cell and the postsynaptic cell.
2) It is worth noting that not all dendrites receive
synaptic input. For example, the dendrites of many sensory
neurons are sensory endings that transduce signals from the
external environment, such as mechanical or chemical stimuli.
These sensory stimuli induce receptor potentials in the dendrite
analogous to the synaptic potentials generated at the synapse.
Regardless of whether they receive sensory or synaptic input, the
dendrites are effectively the antennae of neurons. The dendritic
branching pattern varies to a great extent with the neuronal
type, and is an important determinant of the synaptic or sensory
input received by a neuron.
3) Dendrites pose some extremely interesting problems from
several different perspectives. From the developmental biological
point of view, the dendrite branching pattern is a hallmark of
neuronal type. Even neighboring neurons may exhibit strikingly
different dendritic branching patterns. For example, on the basis
of the dendritic branching pattern alone, the amacrine cells (one
class of interneurons) in the rabbit retina can be subdivided
into at least 20 different subtypes. By extrapolation, using
solely dendrite morphology as a criterion, one could easily
define hundreds or thousands of different types of neurons in the
mammalian central nervous system.
4) From the cell biological point of view, the elaborate and
stereotyped dendritic branching of a neuron is a striking example
of pattern formation and morphogenesis. For example, a Purkinje
cell in the cerebellum can elaborate remarkably complex yet
stereotyped dendrites, and the cellular mechanisms controlling
the formation of these elaborate cellular structures are likely
to have some unique features and differ substantially from those
regulating the formation of other highly branched structures such
as the trachea or blood vessels, since those tubular structures
are formed by the collaboration of multiple cells, each with
simpler morphology.
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Genes & Dev. 2001 15:2627
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SCIENCE-WEEK 15 Feb 2002 www.scienceweek.com
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Related Background:
ON THE COMPLEX FUNCTIONALITY OF NERVE CELL DENDRITES
D-S. Wei et al (University of Maryland, US) discuss the dendrites
of neurons. Dendrites are not passive antennae that simply
receive synaptic inputs: instead, dendrites actively process and
transform inputs as they are received. The apical dendritic arbor
can be divided into 3 morphologically distinct regions: the thick
main apical trunk, a set of short intermediate branches, and a
set of long and thin terminal branches. The apical trunk of
pyramidal cell dendrites is relatively thick and contains
sufficient densities of sodium channels to mediate forward and
backward propagation of action potentials. Terminal branches, in
contrast, have diameters one-fourth that of the apical trunk and
do not decrease over distance. Terminal dendritic segments
constitute 70 to 90 percent of the combined length of the apical
dendritic arbor. Despite being the main recipient of excitatory
synaptic inputs, little is known about the passive and active
transformations an individual terminal segment performs on its
inputs. The authors report that the excitability of terminal
apical dendrites in pyramidal cells of the rat hippocampus
differs from that of the apical trunk. In response to
fluorescence-guided focal photolysis of caged glutamate,
individual terminal apical dendrites generated cadmium-sensitive
all-or-none responses that were subthreshold for somatic action
potentials. Calcium transients produced by all-or-none responses
were not restricted to the sites of photolysis, but occurred
throughout individual distal dendritic compartments, indicating
that electrogenesis is mediated primarily by voltage-gated
calcium channels. The authors suggest that compartmentalized and
binary behavior of parallel-connected terminal dendrites can
greatly expand the computational power of a single neuron.
-----------
Science 2001 293:2272
SCIENCE-WEEK 2001 7 Dec
----------
Related Background:
EVIDENCE FOR COMPUTATIONAL FUNCTION OF NEURON DENDRITES
Compared to the cells of other tissues, nerve cells exhibit
extreme variation in shape (morphology), and one of the central
problems of neurobiology is to relate the shapes of various types
of nerve cells to specific functions (see the background material
below). The auditory system of mammals is one of the better
characterized neurophysiological systems, investigated for more
than a century, and with certain parts of the system exquisitely
defined by experimental procedures. The basic function of the
auditory system of mammals is to receive and analyze input sound
vibrations, and one cardinal aspect is sound localization. In the
auditory regions of the brainstem, there are neurons that act as
"coincidence detectors" -- binaural neurons that respond
maximally when they receive simultaneous inputs from the two
ears, and these neurons are an essential part of the analytical
system responsible for sound localization by the brain.
Essentially, coincidence-detector neurons in the auditory
brainstem of mammals and birds use interaural time differences to
localize sounds, each neuron receiving many narrow-band inputs
from both ears and comparing the time of arrival of the inputs
with an accuracy of 10 to 100 microseconds. Neurons that receive
low-frequency auditory inputs (up to approximately 2 kHz) have
bipolar dendrites (see discussion of dendrites in background
material below), and each dendrite receives inputs from only one
ear. ... ... Agmon-Snir et al (3 authors at 2 installations, US)
now present a simple model that mimics the essential features of
the known electrophysiology and geometry of these bipolar
coincidence detector neurons, and they report that the model
supports the idea that dendrites improve the coincidence
detection properties of these cells, enriching the "computational
power" of these neurons beyond that expected from model neurons
lacking dendrites. The significance of this research is that it
relates in a highly quantitative manner the relation between the
modeled dendritic morphology of a particular type of nerve cell
and its function, and the authors suggest their approach might be
used as a paradigm for the study of dendritic morphology-function
relations in other types of nerve cells.
-----------
Nature 1998 393:268
ScienceWeek 1998 19 Jun
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Related Background:
ON VISUAL CORTEX ASYMMETRICAL LATERAL DENDRITES
Neurons exist with an enormous variety of extension
architectures, but in general they have one axon (which may
branch extensively) and many dendrites leading from the cell body
(which may also branch extensively). Again, in general, axons
conduct nerve impulses away from the cell body, and dendrites
conduct various types of electrical changes toward the cell body.
One of the central problems of neurobiology is to relate the
specific architecture of specific neuron types to neuron
function.
... ... David Ferster (Northwestern University, US) reviews the
work of Margaret Livingston on the function of the curiously
shaped Meynert cells in the visual cortex. Meynert cells are
large pyramidal neurons distinguished by a set of long basal
dendrites that project laterally in one direction for as much as
0.7 mm. Livingston proposes that the asymmetrical dendrites make
Meynert cells sensitive to visual motion, and in particular to
motion in one direction. Livingston's experiments involved
electrophysiological recordings from neurons in the visual cortex
of macaque monkeys. Ferster suggests that if Livingston's cells
are indeed Meynert cells or neurons with asymmetrical dendritic
projections, these cells would become one of the few types of
neurons in the cerebral cortex whose distinctive dendritic
morphology can be assigned a specific visual function.
-----------
Neuron 1998 20:509 1998
Nature 1998 2 April
ScienceWeek 1998 17 Apr
-----------
Related Background:
RETROGRADE AND ANTEROGRADE CONDUCTION IN NEURON DENDRITES
Nerve cells, in biological systems which have nerve cells, come
in all shapes and sizes, with the various shapes and sizes
correlated or not yet correlated with various functions. The
generalized neuron is more or less modeled after the vertebrate
motor neuron, a nerve cell with a particular morphology and a
particular relation of its morphology to its function, but all
neurobiologists are aware of the multiplicities of nerve cell
design actually found in nature, and the multiplicities of the
way various types of nerve cell behave. In the classical
generalized neuron, the idea is that the various membrane
depolarizations and hyperpolarizations that are the inputs to the
neuron are summated as excitatory and inhibitory inputs with an
end result at the initial segment of the axon hillock just beyond
the cell body that determines whether the nerve cell fires an
action potential that will be propagated along its axon to
another neuron or to a muscle cell. This paradigm is the classic
paradigm, supremely useful as a conceptual scheme (and a scheme
that produced at least 4 Nobel Prizes), but the fact is many
neuron types, particularly in the vertebrate brain, are
exceptions to the generalization. This may be particularly true
of the dendritic arborizations of central nervous system neurons,
and one of the fundamental questions of neurobiology is to
unravel the electrophysiology of nerve cell dendrites, and in
particular to determine if and when dendrites of particular types
of neurons actually conduct action potentials. Now Wei R. Chen et
al (3 authors at 2 installations, US, DK) report that
electrophysiological observations of the rat olfactory mitral
nerve cell indicate that the action potential can be initiated
either in the soma-axon hillock or in the distal primary
dendrite, and that the initiation site is controlled by
excitatory synaptic inputs to the distal dendrite and inhibitory
synaptic inputs near the cell body. The authors suggest that
mitral cells provide a model that widens the view of how
dendritic excitability contributes to information processing in
different types of neurons in the vertebrate brain.
-----------
Science 1997 17 Oct
ScienceWeek 1997 7 Nov
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SCIENCE-WEEK 15 Feb 2002 www.scienceweek.com
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13. SELF-ASSEMBLY AND MINERALIZATION OF NANOFIBERS
J.D. Hartgerink et al (Northwestern University, US) discuss
nanofibers, the authors making the following points:
1) Self-assembly and biomineralization are used in
biological systems for natural fabrication of many composite
materials. Bone tissue is a particularly complex example of such
a composite because it contains multiple levels of hierarchical
organization. At the lowest level of his hierarchy is the
organization of collagen fibrils with respect to hydroxyapatite
crystals. The collagen fibrils are formed by self-assembly of
collagen triple helices and hydroxyapatite crystals grow within
these fibrils in such a way that their (c) axes are oriented
along the long axes of the fibers.
2) The preparation of any material with structure on the
nanoscale is a challenging problem. Fabrication of materials that
resemble bone, even at the lowest level of hierarchical
organization, is even more difficult because it involves two
dissimilar organic and inorganic nanophases that have a specific
spatial relation with respect to one another. One way to
accomplish this in an artificial system is to prepare an organic
nanophase designed to exert control over crystal nucleation and
growth of the inorganic component.
3) The authors report they have used the pH-induced self-
assembly of a peptide-amphiphile to make a nanostructured fibrous
scaffold reminiscent of the extracellular matrix of living
tissue. The design of this peptide-amphiphile allows the
nanofibers to be reversibly cross-linked to enhance or decrease
mineralization of hydroxyapatite to form a composite material in
which the crystallographic (c) axes of hydroxyapatite are aligned
with the long axes of the fibers. This alignment is the same as
that observed between collagen fibrils and hydroxyapatite
crystals in bone.
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Science 2001 294:1684
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SCIENCE-WEEK 15 Feb 2002 www.scienceweek.com
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14. ON METAL-CONTAINING POLYMERS
Ian Manners (University of Toronto, CA) discusses metal-
containing polymers, the author making the following points:
1) The valuable physical and chemical properties of many
solids can be attributed to metallic elements. Examples include
magnetic materials used in data storage, superconductors,
electrochromic materials, and catalysts. It has long been
recognized that incorporation of metal atoms into the 1-
dimensional chains of synthetic polymers may also lead to
desirable properties. However, difficulties in synthesis of
macromolecular chains in which metal atoms act as a key
structural component have previously slowed progress in this
field.
2) However, during the past decade, these difficulties in
synthesis have been overcome through the discovery of ring-
opening polymerization and metal-catalyzed polycondensation
methods, and substantial progress has now been made toward the
generation of hybrid metal/polymer materials with novel and
useful properties. Self-assembly is emerging as a powerful tool
to create supramolecular metal-containing polymeric structures,
the approach helping to create self-organized functional
materials whose properties complement those of purely organic
systems.
3) The first metal-containing polymers were materials with
metallic substituents in polymer side chains. Related polymers
with osmium complexes attached to the polymer side chains have
recently attracted attention, and thin films of osmium polymers
can be used to mediate electron transfer or "wire" enzymes such
as glucose oxidase to electrodes. Such systems have allowed the
creation of glucose sensors. In addition, enzyme-based devices
containing related osmium polymers are able to detect a single
base pair mismatch in an 18-base oligonucleotide.
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Science 2001 294:1664
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SCIENCE-WEEK 15 Feb 2002 www.scienceweek.com
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15. ON LONG-DISTANCE QUANTUM COMMUNICATION
L-M. Duan et al (University of Innsbruck, AT) discuss quantum
communication, the authors making the following points:
1) In general, the goal of quantum communication is to
transmit quantum states between distant sites. Such transmission
has potential application in the secret transfer of classical
messages by means of quantum cryptography, and is also an
essential element in the construction of quantum networks. The
basic problem of quantum communication is to generate nearly
perfect entangled states between distant sites. Such entangled
states can be used, for example, to implement secure quantum
cryptography, and to faithfully transfer quantum states via
quantum teleportation.
2) All realistic schemes for quantum communication are
currently based on the use of photonic channels. However, the
degree of entanglement generated between two distant sites
normally decreases exponentially with the length of the
connecting channel, because of optical absorption and other
channel noise. To retain a high degree of entanglement,
purification schemes can be used, but this does not fully solve
the long-distance communication problem. Because of the
exponential decay of the entanglement in the channel, an
exponentially large number of partially entangled states are
needed to obtain one highly entangled state, which means that for
a sufficiently long distance the task becomes nearly impossible.
3) The authors describe a scheme that allows the
implementation of robust quantum communication over long lossy
channels. The scheme involves laser manipulation of atomic
ensembles, beam splitters, and single-photon detectors with
moderate efficiencies, and is therefore compatible with current
experimental technology. The authors demonstrate that the
communication efficiency scales polynomially with the channel
length, and thus the scheme should be operable over very long
distances.
-----------
Nature 2001 414:413
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SCIENCE-WEEK 15 Feb 2002 www.scienceweek.com
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Related Background:
QUANTUM ENTANGLEMENT AND QUANTUM OPTICS
Paul Kwiat (University of Illinois Urbana-Champaign, US)
discusses quantum entanglement. Quantum entanglement between two
particles means that measuring the behavior of one particle
instantly determines the behavior of the other particle, even
when they are physically far apart. Erwin Schroedinger (1887-
1961) once described this peculiar connection as "_the_
characteristic trait of quantum mechanics, the one that enforces
its entire departure from classical lines of thought."
Entanglement describes a system with several components in which
the individual parts carry no information but nevertheless share
quantum correlations with each other that are stronger than those
allowed by classical physics. For example, photons can be
polarized -- the polarization describes the oscillation direction
of the electric field associated with a light wave. Polarization
filters, such as Polaroid sunglasses, will let through photons
polarized in one plane but block those polarized at right angles,
and so can be used to measure photon polarization. If two photons
have entangled polarizations, each photon individually would
appear completely unpolarized (with no particular oscillation
direction) and yet measuring the polarization of one completely
determines to polarization of the other. It is as if you flipped
two coins, each of which was equally likely to come up heads or
tails, and yet they always gave the same results -- that is,
both heads or both tails. Although normal coins do not behave
like this, it has been known for some time how to produce pairs
of photons that do display such bizarre quantum-mechanical
correlations.
-----------
Nature 2001 412:866
SCIENCE-WEEK 2001 28 Dec
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Related Background:
ENTANGLEMENT, DECOHERENCE, AND THE QUANTUM-CLASSICAL BOUNDARY
Quantum mechanical entanglement is a phenomenon that has caught
the imagination of the public as one of the more bizarre
consequences of fundamental physical theory. Entanglement is
unique to quantum mechanics, and involves a relationship (a
"superposition of states") between the possible quantum states of
two entities such that when the possible states of one entity
collapse to a single state as a result of suddenly imposed
boundary conditions, a similar and related collapse occurs in the
possible states of the entangled entity no matter where or how
far away the entangled entity is located. Entanglement arises
from the wave function equation of quantum mechanics, which has
an array of possible function solutions rather than a single
function solution, with each possible solution describing a set
of possible probabilistic quantum states of the physical system
under consideration. Upon fixation of the appropriate boundary
conditions, the array of possible solutions collapses into a
single solution. For many quantum mechanical physical systems,
the fixation of boundary conditions is a theoretical and
fundamental consequence of some interaction of the physical
system with something outside that system, e.g., an interaction
with the measuring device of an observer. In this context, two
entities that are described by the same array of possible
solutions to the wave function equation are said to be
"coherent", and when events decouple these entities, the
consequence is said to be "decoherence". As a physical
phenomenon, entanglement was discussed many years ago, most
particularly following the publication in 1935 of the often
quoted Einstein-Podolsky-Rosen paper (*Physical Review* 1935
47:777). These discussions have been in the form of "gedanken"
(thought) experiments involving two quantum-mechanical entangled
entities. More recently, however, there have been laboratory
constructions of actual quantum mechanical systems exhibiting
such entanglement phenomena, and the reportage of these
laboratory arrangements by the media have engaged the public
fancy. Essential here is that any purely verbal account of
quantum mechanical phenomena is severely limited by the
constraint that the properties of quantum mechanical systems can
be precisely described only by the equations relevant for those
systems, and all other descriptions usually introduce serious
ambiguities. ... ... Serge Haroche (Ecole Normale Superieure
Paris, FR) reviews quantum mechanical entanglement, decoherence,
and the question of the boundary between the physics of quantum
phenomena and the physics of classical phenomena. Haroche makes
the following points: 1) In quantum mechanics, a particle can be
delocalized (simultaneously occupy various probable positions in
space), can be simultaneously in several energy states, and can
even have several different identities at once. This apparent
"weirdness" behavior is encoded in the wave function of the
particle. 2) Recent decades have witnessed a rash of experiments
designed to test whether nature exhibits implausible nonlocality.
In such experiments, the wave function of a pair of particles
flying apart from each other is entangled into a non-separable
superposition of states. The quantum formalism asserts that
detecting one of the particles has an immediate effect on the
other, even if they are very far apart, even far enough apart to
be out of interaction range. The experiments clearly demonstrate
that the state of one particle is always correlated to the result
of the measurement performed on the other particle, and in just
the strange way predicted by quantum mechanics. 3) An important
question is: Why and how does quantum weirdness disappear
(decoherence) in large systems? In the last 15 years, entirely
solvable models of decoherence have been presented by various
authors (e.g., Leggett, Joos, Omnes, Zeh, Zurek), these models
based on the distinction in large objects between a few relevant
macroscopic observables (e.g., position or momentum) and an
"environment" described by a huge number of variables, such as
positions and velocities of air molecules, number of black-body
radiation photons, etc. The idea of these models, essentially, is
that the environment is "watching" the path followed by the
system (i.e., interacting with the system), and thus effectively
suppressing interference effects and quantum weirdness, and the
result of this process is that for macroscopic systems only
classical physics obtains. 4) In mesoscopic systems, which are
systems between macroscopic and microscopic dimensions,
decoherence may occur slowly enough to be observed. Until
recently, this could only be imagined in a gedanken experiment,
but technological advances have now made such experiments real,
and these experiments have opened this field to practical
investigation.
-----------
Physics Today 1999 July
Science-Week 1998 17 Jul
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Related Background:
EXPERIMENTAL QUANTUM TELEPORTATION
Quantum teleportation is the transmission and reconstruction over
arbitrary distances of the state of a quantum system, an effect
first suggested by Bennett et al in 1993 (Phys. Rev. Lett.
70:1895). The achievement of the effect depends on the phenomenon
of entanglement, an essential feature of quantum mechanics.
Entanglement is unique to quantum mechanics, and involves a
relationship (a "superposition of states") between the possible
quantum states of two entities such that when the possible states
of one entity collapse to a single state as a result of suddenly
imposed boundary conditions, a similar and related collapse
occurs in the possible states of the entangled entity no matter
where or how far away the entangled entity is located.
Polarization is essentially a condition in which the properties
of photons are direction dependent, a condition that can be
achieved by passing light through appropriate media. Bouwmeester
et al (6 authors, Univ. of Innsbruck, AT) now report an
experimental demonstration of quantum teleportation involving an
initial photon carrying a polarization that is transferred to one
of a pair of entangled photons, with the polarization-acquiring
photon an arbitrary distance from the initial one. The authors
suggest quantum teleportation will be a critical ingredient for
quantum computation networks.
-----------
Nature 1997 11 Dec
Science-Week 1998 2 Jan
-----------
Related Background:
REPORT OF FIRST QUANTUM MECHANICAL ENTANGLEMENT OF ATOMS
... In the past, evidence of quantum mechanical entanglement has
been restricted to elementary particles such as protons,
electrons, and photons. Now E. Hagley et al, using rubidium
atoms prepared in circular Rydberg states (which means the outer
electrons of the atom have been excited to very high energy
states and are far from the nucleus in circular orbits), have
shown quantum mechanical entanglement at the level of atoms.
What is involved is that the experimental apparatus produces two
entangled atoms, one atom in a ground state and the other atom
in an excited state, physically separated so that the
entanglement is non-local, and when a measurement is made on one
atom, let us say the atom in a ground state, the other atom
instantaneously presents itself in the excited state -- the
result of the second atom wave function collapse thus determined
by the result of the first atom wave function collapse. There is
talk that before long quantum mechanical entanglement may be
demonstrated for molecules and perhaps even larger entities.
-----------
Phys. Rev. Lett. 1997 79:1
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Related Background:
QUANTUM PHOTON ENTANGLEMENT AT A DISTANCE OF SEVEN MILES
Whether or not the quantum mechanical behavior of elementary
particles is called mysterious depends, more or less, on the
attitude one has. If there is a demand that the behavior of these
particles be explainable with the logistic structure of human
language, then some aspects of their behavior seem mysterious
indeed. On the other hand, if there is a willingness to admit
that the logical structure of human language may not at present
be isomorphic with the logical structure of the laws that govern
the behavior of these particles, then it is probably best to put
off notions of mysteries and take the behavior for what it is.
This week there was announced to the popular press, before
publication, the results of a twin-photon experiment in
Switzerland. Nicolas Gisin et al (University of Geneva, CH)
reported that a pair of twin photons split and sent along two
diverging paths, when arriving at terminals seven miles apart,
exhibit the phenomenon of quantum "entanglement". The gist of it
is that the detection of one of the photons effectively causes
the collapse of the spectrum of its wave-function solutions to a
single solution, and this collapse instantaneously causes the
collapse of the possible quantum states of the other photon, in
this case seven miles away. The melodramatic notion (purveyed by
the press) is that information has somehow travelled from one
photon to the other at a speed greater than the speed of light,
with the result that great canons of thought are thereby
destroyed. But perhaps the more prosaic reality is that any
attempt to describe non-classical events with language based on
classical laws and perceptions cannot succeed.
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ScienceWeek 1997 25 Jul
New York Times 1997 22 Jul
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SCIENCE-WEEK 15 Feb 2002 www.scienceweek.com
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16. A COMPUTING MACHINE MADE OF BIOMOLECULES
Y. Benenson et al (Weizmann Institute of Science, IL) discuss
biomolecule computing machines, the authors making the following
points:
1) Devices that convert information from one form into
another according to a definite procedure are known as
"automata". One such hypothetical device is the "universal Turing
machine", which stimulated work leading to the development of
modern computers. The Turing machine and its special cases,
including finite automata, operate by scanning a data tape, whose
striking analogy to information-encoding biopolymers has inspired
several designs for molecular DNA computers. Laboratory-scale
computing using DNA and human-assisted protocols has been
demonstrated, but the realization of computing devices operating
autonomously on the molecular scale remains rare.
2) The authors describe a programmable finite automaton
comprising DNA and DNA-manipulating enzymes that solves
computational problems autonomously. The automaton's hardware
consists of a restriction nuclease and ligase, the software and
input are encoded by double-stranded DNA, and programming amounts
to choosing appropriate software molecules. Upon mixing solutions
containing these components, the automaton processes the input
molecule via a cascade of restriction, hybridization, and
ligation cycles, producing a detectable output molecule that
encodes the automaton's final state, and thus the computational
result. In this implementation, 10^(12) automata sharing the same
software run independently and in parallel on inputs (which could
in principle be distinct) in a 120 microliter solution at room
temperature at a combined rate of 10^(9) transitions per second
with a transition fidelity greater than 99.8 percent, consuming
less than 10^(-10) watts.
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Nature 2001 414:430
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Related Background: COMPUTER SCIENCE: ALAN TURING
In 1936, the mathematician Alan M. Turing (1912-1954) proposed
consideration of an abstract computer that subsequently came to
be known as a "Turing machine". Essentially, the simplest Turing
machine system consists of a movable input tape, a black box (the
Turing machine) that reads the tape according to an internal
algorithm, and an output tape that records the output of the
black box. The machine originally considered by Turing was a bit
more complex, with a single input/output tape demarcated into
discrete small sections, and the machine capable of being in any
one of a set of states (determined by the algorithm or "Rule
Set") according to which section of the tape the machine happened
to be reading, and the output capable of moving the tape backward
or forward. As a mathematician, Turing's interest was to
determine the universe of problems capable of being solved by
such a machine, and his ideas have been of considerable influence
in both mathematical and engineering theories of computing
machines. Turing was also interested in several biological
problems, and to a number of mathematically inclined
biologists the Turing machine in its simplest form has been for
many decades an intriguing model for certain computational
processes in the nervous system. More recently, in molecular
biology, the Turing machine has been recognized as an analog of
the behavior of nucleic acid polymerases such as DNA polymerase
and RNA polymerase (enzymes which catalyze the formation of
nucleic acid polymers), which sequentially synthesize an output
polymer (output tape) according to the sequential reading of the
individual units of an input polymer (input tape). Also of
interest to neural systems researchers has been a little-known
paper by Turing on learning behavior of artificial neural
networks not published until 14 years after his death.
... ... B.J. Copeland and D. Proudfoot (University of Canterbury,
NZ) present a biographical essay on Alan Turing, the authors
making the following points:
1) All current digital computers are essentially Turing
machines. Turing also pioneered the field of artificial
intelligence, proposing the widely debated "*Turing test" as a
method of determining whether a suitably programmed computer
exhibits "intelligence" (i.e., can "think"). During World War II,
as part of a British intelligence unit, Turing was instrumental
in breaking the German "Enigma" code, a feat that has been said
to have shortened the war by two years. At the end of his short
life, Turing was engaged in the earliest work on what would now
be called "artificial life", his research involving simulation of
the chemistry of biological growth.
2) Throughout his career, Turing had no great interest in
publicizing his ideas, and as a consequence important aspects of
his work have been neglected or forgotten over the years. In
particular, few people are familiar with Turing's anticipation of
"connectionism" or neuron-like computing. Also neglected are his
groundbreaking theoretical concepts in the area of
"hypercomputation", a field devoted to the computational solution
of apparently intractable problems.
-----------
Scientific American 1999 April
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Notes:
... ... *Turing test: The Turing test is essentially a protocol
for distinguishing between real (human) thought and simulated
(computer) thought. A classic statement of the Turing test is as
follows: One room contains a person and another room contains a
machine. An interrogator in a third room asks questions of both
in an attempt to identify them. When the interrogator cannot
distinguish between them by questioning, the machine can be said
to possess human-like intelligence. [Editor's note: There are
aspects of the test as thus stated which are ill-defined. For
example, there is no operational definition of "intelligence".
Secondly, in terms of procedure, the test is perhaps more useful
when amended as follows: If a determined questioner can find no
question that can enable absolute identification of the machine,
then it can be concluded that, in the frame of reference of the
questioner, the analytical processes of the machine are at least
qualitatively equivalent to the analytical processes of the
human.]
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SCIENCE-WEEK 1999 9 Jul
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Related Background:
ON COMPUTING WITH DNA
... ... Leonard M. Adleman (University of Southern California,
US) presents an essay on a computing ensemble involving DNA, the
ensemble based on the author's recognition of the Turing machine
as an analog of DNA polymerase, and the ensemble applied to the
solution of a mathematical problem known as the "Hamiltonian Path
Problem". As a mathematician and computer scientist, Adleman's
objective is the demonstration that his DNA ensemble can perform
as a powerful computer and solve a posed mathematical problem.
The author considers the following as the tools of a potential
DNA computing system: *Watson-Crick pairing, *polymerases,
*ligases, *nucleases, *gel electrophoresis, DNA synthesis, and
the *polymerase chain reaction. The author presents the
Hamiltonian Path Problem as follows: Given a graph with directed
edges and a specified start vertex and end vertex, one says there
is a Hamiltonian path if and only if there is a path that starts
at the start vertex, ends at the end vertex, and passes through
each remaining vertex exactly once. The Hamiltonian Path Problem
is to decide for any given graph with specified start and end
vertices whether a Hamiltonian path exists or not. The specific
problem chosen by the author involves a 7-vertex graph. Each
vertex is identified by a specific assigned sequence of nucleic
acid bases, and using the repertoire of biochemical tools
indicated above (and an added auxiliary separation technique),
the author demonstrates that this particular problem is easily
solved. Considering molecular computers, the author points out
their advantages: 1) The possibility of extremely dense
information storage. "For example, one gram of DNA, which when
dry would occupy a volume of approximately one cubic centimeter,
can store as much information as approximately 10^(9) CDs." 2)
The possibility for enormous parallelism. In the author's
problem, approximately 10^(14) connection paths were
simultaneously concatenated in about 1 second. 3) Extraordinary
energy efficiency. In principle, 1 joule is sufficient for
approximately 2 x 10^(19) DNA ligation operations. The author
suggests that his experiment "can be viewed as a manifestation of
an emerging new area of science made possible by our rapidly
developing ability to control the molecular world."
-----------
Scientific American 1998 August
ScienceWeek 31 Jul 98
-----------
Notes:
... ... *Watson-Crick pairing: Also known as complementary base
pairing. This refers to the specific chemical affinities between
specific base pairs in a nucleic acid: adenine always pairs with
thymine, and guanine always pairs with cytosine. In pairing
between DNA and RNA, the uracil of RNA always pairs with adenine.
Complementary base pairing is not only responsible for the DNA
double helix, but it is also essential for various in vitro
techniques such as PCR (*polymerase chain reaction).
... ... *polymerases: Refers to any enzyme that directs the
synthesis of a polymer by linking individual monomers. Examples
in biological systems are DNA polymerase and RNA polymerase.
... ... *ligases: Ligases are enzymes that catalyze the stitching
together of polymer fragments. DNA ligase, for example, catalyzes
phosphodiester bond formation between two DNA fragments, and this
enzyme is involved in normal DNA replication, repair of damaged
chromosomes, and various in vitro techniques in genetic
engineering that involve linking DNA fragments.
... ... *nucleases: Refers to any enzyme that acts on nucleic
acids, e.g., DNase, RNase, endonuclease, etc.
... ... *gel electrophoresis: In general, electrophoresis is a
laboratory technique used to separate macromolecules on the basis
of electric charge and size, the technique involving application
of an electric field to a population of macromolecules dispersing
according to their electric mobilities. In gel electrophoresis,
the porous medium through which the macromolecules move is a gel.
... ... *polymerase chain reaction (PCR): A technique for
isolating and amplifying any specifically desired DNA sequence.
The reaction is facilitated by a heat-stable DNA polymerase
(e.g., Taq, which is obtained from a thermophilic bacterium) that
can withstand the many cycles of heating and cooling involved in
the technique. PCR is considered by many molecular biologists to
be the most important technical advance in molecular biology in
the second half of the 20th century. The inventor of the
technique, Kary Mullis, received the Nobel Prize in Chemistry in
1993 for his discovery.
-----------
SCIENCE-WEEK 1998 31 Jul
PRAXIS 2002 28 Jan
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SCIENCE-WEEK 15 Feb 2002 www.scienceweek.com
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17. ON THE PACKING OF SPHERICAL GRANULAR MATERIAL
A.J. Forsyth et al (Monash University, AU) discuss the packing of
spherical granular material, the authors making the following
points:
1) While there has been a recent upsurge of interest in
granular materials among physicists, the study of granular
packing has a long history dating back as far as Johannes Kepler
(1571-1630). In addition to its theoretical interest,
understanding how particle properties affect packing arrangements
in powders is of great practical importance. Examples range from
the formation of tablets from complex particulate mixtures in the
pharmaceutical industry to manufacture of sintered metal products
from metal powders to the apparently simple task of ensuring that
25 kg of a powder product will fit into a 25 kg bag for
distribution and sale.
2) The "void fraction" (ratio of the volume occupied by
voids to the volume occupied by voids plus particles) in packed
particulate materials is affected by particle size distribution,
particle shape, and interparticle forces. In general, for random
packing arrangements, void fraction decreases with increasing
width of size distribution, increased particle sphericity, and
decreasing interparticle cohesive forces. Industrially relevant
interparticle cohesive forces may appear as van der Waals forces
in dry powders or liquid bridges forces in damp powders.
3) In the absence of interparticle forces, a powder will
attain a void fraction somewhat between the loose random packing
limit (approximately 0.42) and the dense random packing limit
(approximately 0.37). Interparticle forces allow "vaulting" to
occur, leading to large (on the scale of the particles) voids
within the powder, and thus a greater void fraction. It is well
known that in dry powders the range of possible packing densities
under normal gravity increases with decreasing particle size.
-----------
Phys. Rev. Lett. 2001 87:244301
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SCIENCE-WEEK 15 Feb 2002 www.scienceweek.com
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18. TWO-LEVEL JOSEPHSON-JUNCTION SYSTEMS IN QUANTUM COMPUTING
A thin insulating barrier separating two superconducting
materials at low temperature is called a "Josephson junction",
and superconducting current can flow across the junction in the
absence of an applied voltage (direct-current Josephson effect).
When the current exceeds a critical value, the zero-resistance
character of the barrier is lost. Such a junction has a number of
interesting properties when subjected to various applied fields.
So-called "Josephson effects" were predicted theoretically by
B.D. Josephson in 1962. Josephson was 22 years of age when he
made his theoretical discovery; he received the Nobel Prize in
Physics in 1973.
... ... Y. Nakamura et al (NEC Laboratories, JP) discuss two-
level Josephson-junction systems, the authors making the
following points:
1) A two-level system is a simple model widely applied to
many problems in physics. For decades, time evolution of the
quantum state of a two-level system has been extensively studied
in many contexts: e.g., nonadiabatic transition at the level
crossing, quantum state evolution under a resonant driving field
(Rabi oscillations), and the effect of a dissipative environment
coupled to the two-level system. Moreover, recent proposals for
implementations of quantum computation, which require coherent
control of the quantum state of a two-level system, i.e., a
"qubit", have increased the interest in the dynamic behavior of a
two-level system under a driving force such as an oscillation
field or a high-speed pulse.
2) One of the candidates for physical realization of a qubit
is a small Josephson-junction circuit called a "Cooper-pair box",
which consists of a small superconducting electrode connected to
a reservoir via a Josephson junction. Because of the charging
effect of the small electrode, two charge-number states, in which
the number of Cooper pairs in the "box" electrode differs by one,
constitute an effective two-level system. Because of the
collective nature of the superconducting state, this two-level
system is basically characterized simply by "macroscopic"
parameters, the Josephson energy and the charging energy, which
can be well controlled by the geometry of the circuit designed
and fabricated by present nanotechnology. Superposition of the
two charge states has been confirmed in experiments, and coherent
manipulation of the quantum state by using a dc gate-voltage
pulse has been demonstrated, i.e., coherent oscillations between
two degenerate charge states were observed.
-----------
Phys. Rev. Lett. 2001 87:246601
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SCIENCE-WEEK 15 Feb 2002 www.scienceweek.com
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19. EPSTEIN-BARR VIRUS AND MULTIPLE SCLEROSIS
A. Ascherio et al (Harvard University, US) discuss Epstein-Barr
virus and multiple sclerosis, the authors making the following
points:
1) The etiology of multiple sclerosis is largely unknown,
but evidence supports the idea of an autoimmune process triggered
by infection or other environmental factors. Epstein-Barr virus,
a herpesvirus, infects more than 90 percent of the human
population, establishing a persistent and highly immunogenic
infection of B lymphocytes. The population of antigen-specific
cytotoxic T cells is massively expanded in response to primary
infection and persists at high levels for several years.
Autoimmunity could result if some of these cells carry T-cell
receptors that recognize self-peptides. Epstein-Barr virus has
been related to nasopharyngeal carcinoma, Burkitt lymphoma, and
Hodgkin disease, and a relation to autoimmune diseases has been
proposed by remains unproven.
2) Infection with Epstein-Barr virus is usually asymptomatic
in childhood but frequently causes infectious mononucleosis in
adolescents and adults. The similarity in the epidemiology of
multiple sclerosis and infectious mononucleosis led to the
proposition that multiple sclerosis could be caused by infection
with Epstein-Barr virus during or after adolescence in
genetically susceptible individuals. This hypothesis is supported
by observations suggesting an increased risk of multiple
sclerosis following infectious mononucleosis, the rarity of
multiple sclerosis among individuals without serum anti-Epstein-
Barr virus antibodies, and the higher serum titers of anti-
Epstein-Barr virus antibodies in multiple sclerosis patients than
in controls.
3) The authors report a prospective study of the role of
Epstein-Barr virus in the etiology of multiple sclerosis, the
study involving examination of the association between serum
anti-Epstein-Barr virus antibody titers and risk of developing
multiple sclerosis in 2 large cohorts of US women. The total
number of women in the study was 62,439. The authors report that
their results support a role of Epstein-Barr virus in the
etiology of multiple sclerosis. A 4-fold difference in titers of
antibodies to Epstein-Barr virus antigens was associated with a
4-fold increase in risk of multiple sclerosis.
-----------
J. Am. Med. Assoc. 2001 286:3083
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SCIENCE-WEEK 15 Feb 2002 www.scienceweek.com
----------
Related Background:
MEDICAL BIOLOGY: A POSSIBLE CAUSE OF MULTIPLE SCLEROSIS
In the vertebrate central nervous system, the axons of nerve
cells involved in physiological functions that require rapid
signaling (for example, the neural control of voluntary muscle)
are wrapped in a special sheath called myelin. The myelin sheath
consists of concentric layers of electrically insulating lipid-
protein material, but the sheath is periodically interrupted
along the length of the axon, and at the points where the sheath
is interrupted so is the electrical insulation interrupted. The
result, predictable from the classical physics of electrical
transmission lines and the electrical parameters of nerve fibers,
is that the propagation of an electrical pulse along such nerve
fibers occurs at a velocity much higher than that found in
unmyelinated fibers. Multiple sclerosis is a human disease
characterized by the progressive loss of the myelin of the brain
and spinal cord, with the physiological disruptions to be
expected from such loss, considering the significance of myelin
in the functioning of nerve cells. The cause of the disease is
unknown, but an immunological abnormality is suspected. It has
also been postulated that the cause is infection by a latent
virus, with viral activation and expression triggering a
secondary immune response. There is some evidence for genetic
susceptibility, and there is also evidence that environment may
be a factor, since the disease is 5 times more common in
temperate climates than in the tropics.
... ... D.C. Shields et al (4 authors at 2 installations, US JP)
now present a study of the mechanism of demyelinization in
multiple sclerosis, the authors reporting the following:
1) In autoimmune demyelinating diseases such as multiple
sclerosis, the degradation of myelin proteins results in the
destabilization of the myelin sheath. Protein-degrading enzymes
(proteases, proteinases) have been implicated in myelin protein
degradation, and recent studies have demonstrated increased
expression and activity of a calcium-activated neutral proteinase
(calpain) in experimental allergic encephalomyelitis, the
corresponding animal model of multiple sclerosis.
2) In the present study, calpain activity and expression
were evaluated in white matter from human patients with multiple
sclerosis and Parkinson's and Alzheimer's diseases and compared
with that of white matter from normal controls. Analysis
indicates that the active form of calpain and calpain-specific
degradation products were increased by 90.1 percent and 52.7
percent, respectively, in multiple sclerosis plaques compared
with normal white matter, and that calpain expression increased
by more than a factor of 4 compared with normal white matter.
Calpain activity and expression were not increased significantly
in white matter from patients with Parkinson's or Alzheimer's
diseases compared with that of normal controls.
3) The authors suggest that because calpain degrades all
major myelin proteins, the increased activity and expression of
this proteinase may play a critical role in the degradation of
myelin in autoimmune demyelinating diseases such as multiple
sclerosis.
-----------
Proc. Nat. Acad. Sci. 1999 96:11486
SCIENCE-WEEK 1999 19 Nov
-----------
Related Background:
HERPESVIRUS LINKED TO MULTIPLE SCLEROSIS
In the vertebrate central nervous system, the axons of nerve
cells involved in physiological functions that require rapid
signaling (for example, the neural control of voluntary muscle)
are wrapped in a special sheath called myelin. The myelin sheath
consists of concentric layers of electrically insulating lipid
material, but the sheath is periodically interrupted, and at the
points where the sheath is interrupted so is the electrical
insulation interrupted. The result, predictable from the
classical physics of electrical transmission lines and the
electrical parameters of nerve fibers, is that the propagation of
an electrical pulse along such nerve fibers occurs at a velocity
much higher than that found in unmyelinated fibers. Multiple
sclerosis is a human disease characterized by the progressive
loss of the myelin of the brain and spinal cord, with the
physiological disruptions to be expected from such loss,
considering the significance of myelin in the functioning of
nerve cells. The herpesviruses are a class of viruses producing
the complex of herpes diseases, and HHV-6 is a recently
discovered strain of herpesvirus that apparently causes an infant
and early childhood disease called roseala infantum. Jacobson et
al (National Institutes of Health, US) report that a study of
multiple sclerosis patients (36 patients and 66 controls)
revealed that 70% of these patients were infected with the strain
of herpesvirus HHV-6. They also report that magnetic resonance
imaging detected numerous myelin lesions in the brain of a
deceased multiple sclerosis patient, and an autopsy revealed
HHV-6 in the lesions but not in the adjoining normal tissues.
Some multiple sclerosis specialists are expressing reservations
about the interpretation of these results, stating it is possible
the viral infection is a consequence rather than a cause of
multiple sclerosis.
-----------
Nature Medicine 1997 December
ScienceWeek 1997 26 Dec
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SCIENCE-WEEK 15 Feb 2002 www.scienceweek.com
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20. ON THE RISK OF ATTEMPTED SUICIDE THROUGHOUT THE LIFESPAN
S.R. Dube et al (Centers for Disease Control and Prevention, US)
discuss the relationship between childhood abuse, household
dysfunction, and the risk of attempted suicide throughout the
lifespan, the authors making the following points:
1) Suicide was the 8th leading cause of death in the US in
1998, and particularly high rates have been reported among young
persons and older adults. Each year, more than 30,000 people in
the US commit suicide, but recognition of persons who are at high
risk for suicide is difficult, making efforts to prevent its
occurrence problematic. In 1999, the US surgeon general brought
attention to this complex public health issue by recommending
that the investigation and prevention suicide be a national
priority.
2) An expanding body of research suggests that childhood
trauma and adverse experiences can lead to a variety of negative
health outcomes, including substance abuse, depressive disorders,
and attempted suicide among adolescents and adults. Childhood
sexual and physical abuse have been strongly associated with
suicide attempts. A recent study of Norwegian drug addicts
demonstrated that a high proportion of them attempted suicide and
that an even higher proportion of drug addicts who had
experienced childhood adversity had attempted suicide. In another
study, low-income women with a history of alcohol problems and
experience of childhood abuse and neglect were at increased risk
for suicide attempts.
3) The authors conducted a study to examine the relationship
between the risk of suicide attempts and adverse childhood
experiences and the number of such experiences. 17,337 adult
health maintenance organization members (54 percent female) were
surveyed. The authors report that a strong graded relationship
exists between adverse childhood experiences and risk of
attempted suicide throughout the life span. Alcoholism, depressed
affect, and illicit drug use, which are strongly associated with
such experiences, appear to partially mediate this relationship.
-----------
J. Am. Med. Assoc. 2001 286:3089
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SCIENCE-WEEK 15 Feb 2002 www.scienceweek.com
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21. VERY-LOW-BIRTH-WEIGHT INFANTS 20 YEARS LATER
M. Hack et al (Case Western Reserve University, US) discuss young
adulthood outcomes for very-low-birth-weight infants, the authors
making the following points:
1) The introduction of neonatal intensive care in the 1960s
resulted in substantial improvements in outcomes for very-low-
birth-weight infants (those weighing less than 1500 grams). By
the 1970s, 80 to 90 percent of survivors were reported to be free
of serious handicaps. However, at school age, very-low-birth-
weight children have poorer cognitive function and poorer
academic performance than normal birth-weight controls. Learning
problems at school persist into adolescence and are apparent even
in children who have normal intelligence and no neurological
impairment.
2) Before the era of neonatal intensive care, when few very-
low-birth-weight infants survived, the majority of survivors were
described as having average or above-average mental development.
A more recent report, however, indicated that fewer persons with
birth weights of less than 1000 grams, compared to normal birth-
weight controls, had graduated from high school. Reports from
Europe note that very-low-birth-weight young adults have similar
levels of educational attainment but more chronic illness and
handicap than members of the general population or normal birth-
weight controls.
3) The authors report a longitudinal study of a cohort of
242 survivors among very-low-birth-weight infants born between
1977 and 1979 (mean birth weight 1179 grams; mean gestational age
at birth, 29.7 weeks), with 233 controls from the same population
in Cleveland who had normal birth weights. The authors assessed
educational level, cognitive and academic achievement, and rates
of chronic illness and risk taking behavior at 20 years of age.
The authors conclude that educational disadvantage associated
with very low birth weight persists into early adulthood.
-----------
New Engl. J. Med. 2002 346:149
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SCIENCE-WEEK 15 Feb 2002 www.scienceweek.com
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22. AQUACULTURE AND AQUATIC INVASIVE SPECIES
R.L. Naylor et al (Stanford University, US) discuss aquaculture,
the authors making the following points:
1) Aquaculture -- the farming of fish, shellfish, and
aquatic plants -- is among the fastest-growing segments of the
world food economy. Global aquaculture production more than
doubled in volume and value during the past decade and now
supplies one-third of seafood consumed worldwide. Growth in US
production parallels the global trend. Spread across all 50
states in the US, aquaculture farms collectively raise over 100
different species of aquatic plants and animals.
2) In the US and abroad, aquaculture has led to the
introduction of unwanted seaweeds, fish, invertebrates,
parasites, and pathogens, and without special care, the rapid
expansion of this sector will result in the spread of even more
pests. Aquaculture has become a leading vector of aquatic
invasive species worldwide.
3) Most major aquaculture species cultured in the US are not
native to their farm sites. Accidental escapes and even
deliberate release create "biological pollution" with
irreversible and unpredictable ecological impacts. Surprisingly
little federal oversight exists even for deliberate aquaculture
introductions in the US. For example, no restrictions existed to
prevent the escape of seaweed species introduced in 1973 to
Hawaii, and these species have since spread rapidly across
Hawaii's coral reefs. Likewise, bighead and silver carps,
imported from Asia for confined food culture and biological
control in the 1970s, have become established in rivers
throughout the Mississippi Basin and compete with native fish.
Local and state regulations are inadequate, particularly because
once species escape, they often move across state boundaries.
-----------
Science 2001 294:1655
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SCIENCE-WEEK 15 Feb 2002 www.scienceweek.com
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23. ANALYSIS OF THE UK CREUTZFELDT-JAKOB DISEASE EPIDEMIC
A-J. Valleron et al (Pierre and Marie Curie University, FR)
discuss the UK Creutzfeldt-Jakob disease epidemic, the authors
making the following points:
1) As of 1 May 2001, there were 97 cases of definite (86) or
probable (11) variant Creutzfeldt-Jakob disease in the UK. These
patients probably contracted the disease by oral ingestion of
food contaminated by the agent of bovine spongiform
encephalopathy (BSE) before the UK bovine-specific risk materials
ban in 1989. The number of BSE infected animals is estimated to
have been in the range 900,000 to 1.13 million, with between
460,000 and 482,000 animals slaughtered for consumption before
the introduction of the November 1989 specified offal ban.
2) The epidemic may have started as early as 1980, and the
number of people exposed to potentially infective doses through
food may be extremely high. Therefore, one could pessimistically
assume that virtually everybody in the population has been in
contact with food or bovine products originating from BSE-
infected animals.
3) In summary: The size of the variant Creutzfeldt-Jakob
disease epidemic in the UK is a major public health concern and a
subject of speculation. The cases are young (mean age = 28).
Assuming that the risk of developing the disease in susceptible
exposed subjects decreases exponentially with age after age 15,
that all infections occurred between 1980 and 1989, and that the
distribution of the incubation period is log-normal, the authors
estimate that the mean duration of the incubation period is 16.7
years, and that the total number of cases will be 205.
-----------
Science 2001 294:1726
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SCIENCE-WEEK 15 Feb 2002 www.scienceweek.com
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24. ON UNIVERSITY-INDUSTRY CONNECTIONS
A.C. Gelijns and S.O. Thier (Columbia University, US) discuss
university-industry connections, the authors making the following
points:
1) University-industry research collaborations have been key
to a continued high degree of technological innovation in
medicine. Recently, however, critical questions have been posed
about the potential negative aspects of highly productive means
of encouraging innovation. Concerns center on the blurring of the
interface between academic research and the commercial world, and
the implications of the newfound readiness of universities to
benefit financially from their intellectual property.
2) The roles of both parties are often inadequately captured
by considering members of university faculties as single-mindedly
devoted to the advancement of fundamental knowledge, while
considering industrial firms as mere developers of university
research. Rather, medical innovation depends on extensive
interactions between universities and industry, with knowledge
and technology transfer flowing in both directions.
3) However, there is a risk to the university-industry
relationship if the cultural and ethical principles of one
partner overwhelm those of the other. Therefore, universities and
industry need to maximize the upsides of collaboration and
minimize the downsides by means of internal organizational change
as well the formation of new models of collaboration, such as
intellectual partnerships or virtual research organizations.
-----------
J. Am. Med. Assoc. 2002 287:72
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SCIENCE-WEEK 15 Feb 2002 www.scienceweek.com
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25. POSTDOCTORAL FELLOWSHIP PROFILE:
Laboratory of Wolf-Dietrich Heyer at Univ. of California Davis
--------------------------------------------------------------
INSTALLATION: University of California, Davis
DEPARTMENT: Section of Microbiology
GENERAL RESEARCH AREA: Molecular genetics, biochemistry
HEAD OF THIS SPECIFIC LABORATORY: Wolf-Dietrich Heyer, PhD,
Professor of Microbiology
Postdoctoral fellowships are available in the following
specific research problems: Project 1: Mechanism of DSB repair by
homologous recombination. Biochemical and molecular analysis of
DSB repair proteins using in vivo and in vitro assays. The
present focus is the S. cerevisiae Rad54 and Mus81/MMms4 proteins
and the later steps in the recombination process (branch
migration, resolution) and on the human Brca2 tumor suppressor
protein. For recent publications see: Mazin et al. (2000) Mol.
Cell 6, 583-592; Solinger et al. (2001) JMB 307, 1207-1221;
Solinger & Heyer (2001) Proc. Nat. Acad. Sci. USA 98, 8447-8453;
Haber & Heyer (2001) Cell 107, 551-554. Project 2: Regulation of
DSB repair by DNA damage checkpoints. Biochemical and molecular
analysis of the regulation of the DSB repair protein Rad55 by
phosphorylation and of the activation and function of DNA damage
checkpoint kinases in the yeast S. cerevisiae. For a recent
publication see: Bashkirov et al. (2000) Mol. Cell. Biol. 20,
4393-4404.
PREVIOUS RESEARCH EXPERIENCE AND DEGREES REQUIRED: Required
is a PhD in Genetics, Molecular Genetics, Cell Biology or
Biochemistry with a strong background in molecular biology or
protein biochemistry. Experience in yeast genetics and/or
biochemistry of DNA binding proteins would be a plus, but is not
required. Required is strong motivation and interest in DNA
damage checkpoints, DNA repair, and homologous recombination.
USUAL STARTING STIPEND: According to NIH NRSA level;
presently with no postdoc experience $28,260/yr plus benefits.
APPROXIMATELY NUMBER OF PEOPLE CURRENTLY WORKING IN THIS
SPECIFIC LABORATORY (FACULTY, STAFF, STUDENTS, POSTDOCS): 6
CONTACT FOR MORE INFORMATION: Wolf-Dietrich Heyer
wdheyer@ucdavis.edu Tel. (530) 752-3001
FURTHER RELEVANT INFORMATION: The Heyer laboratory is
located in the Section of Microbiology at UC Davis, one of the
largest University of California campuses with a strong emphasis
in biology. Studies in DNA metabolism are a focus of the
Division of Biological Sciences and ten laboratories are active
in this area. The Heyer laboratory is located in the new Life
Sciences Addition building and state-of-the-art equipment is at
hand. Davis is a friendly college town that provides a safe
environment with a high quality of life at a reasonable cost.
Davis is located 1 hour East of San Francisco and two hours West
of Lake Tahoe and the ski slopes of the Sierra Nevada. For more
information about the Heyer lab, the University of California,
Davis, and the city of Davis, check out:
http://microbiology.ucdavis.edu/heyerlab/wdhhome.htm.
------------------------
Wolf-Dietrich Heyer, PhD
Professor of Microbiology
Section of Microbiology
University of California, Davis
One Shields Avenue
Davis, CA 95616
U.S.A.
--------------------------------------
TEL. +1 530-752-3001 office/ -3016 lab
FAX +1 530-752-3011
Email wdheyer@ucdavis.edu
http://microbiology.ucdavis.edu/heyerlab/wdhhome.htm
--------------------------------------------------------------
Please note: Postdoctoral Fellowship Profiles are provided to
ScienceWeek by the heads of laboratories, and ScienceWeek does
not charge for their publication. For information about
publishing a Postdoctoral Fellowship Profile, contact Claire
Haller at haller@scienceweek.com
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26. IN FOCUS: ON STUDYING FOSSILS (IAN TATTERSALL)
"When I was in graduate school, my office was a desk in a
basement storeroom of a natural history museum. I would watch
enviously as visiting scientists pored for hours over fossils
that they pulled from drawers in the cabinets that lined the
room, making reams of notes and measurements. It seemed that
these people -- these initiates -- knew exactly what they were
doing, while nobody had yet taken the trouble to explain to me
how to go about studying fossils. I had attended innumerable
courses in vertebrate paleontology, of course, but the emphasis
was always on the instructor's interpretation of particular
fossils, and not on how those interpretations were arrived at.
Eventually I plucked up the courage to ask a distinguished
paleoanthropologist what the secret of studying fossils was. The
answer? 'You look at them long enough, and they speak to you.'
Well, yes, okay. It's true that sheer familiarity with fossils
will reveal things about them that nothing else can. But as my
colleague Milford Wolpoff once said, 'I've spent a lot of time
alone with fossils, and none of them ever said a word.' And my
hearing is no better than Milford's. Of course, it's useless to
deny that a largely seat-of-the-pants approach to studying
fossils had brought paleontologists a very long way since the
early 19th century. An intuitive appreciation of anatomical
similarities and how they are distributed among living organisms
had permitted some very smart people to arrive at a remarkably
detailed and accurate description of the diversity of life. But
even as I was receiving my rather dusty answer to my innocent
question, I felt that surely there must be something more than
this in the study of mute fossils. And, of course, there is...
Cladistics... With the advent of cladistics, systematics had
finally acquired a truly scientific basis."
-----------
Ian Tattersall: _The Monkey in the Mirror: Essays on the Science
of What Makes Us Human_
Harcourt, New York 2002, p.21
http://www.amazon.com/exec/obidos/ASIN/0151005206/scienceweek
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27. NEW BOOKS
Morris: Stereochemistry
http://www.amazon.com/exec/obidos/ASIN/085404602X/scienceweek
Medawar: Hitler's Gift: The True Story of the Scientists Expelled
by the Nazi Regime
http://www.amazon.com/exec/obidos/ASIN/1559705647/scienceweek
Harman: The Natural Philosophy of James Clerk Maxwell
http://www.amazon.com/exec/obidos/ASIN/052100585X/scienceweek
Hoffmann: Otto Hahn: Achievement and Responsibility
http://www.amazon.com/exec/obidos/ASIN/0387950575/scienceweek
Beller: Quantum Dialogue: The Making of a Revolution
http://www.amazon.com/exec/obidos/ASIN/0226041816/scienceweek
Greenberg: Science, Money, and Politics: Political Triumph and
Ethical Erosion
http://www.amazon.com/exec/obidos/ASIN/0226306348/scienceweek
Nielsen et al: Quantum Computation and Quantum Information
http://www.amazon.com/exec/obidos/ASIN/0521635039/scienceweek
Benosman et al: Panoramic Vision: Sensors, Theory, and
Applications
http://www.amazon.com/exec/obidos/ASIN/0387951113/scienceweek
McGrayne: Prometheus in the Lab: Chemistry and the Making of the
Modern World
http://www.amazon.com/exec/obidos/ASIN/0071350071/scienceweek
McMichael: Human Frontiers, Environments, and Disease: Past
Patterns, Uncertain Futures
http://www.amazon.com/exec/obidos/ASIN/0521004942/scienceweek
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