ScienceWeek

SCIENCE-WEEK

A Weekly Email Digest of the News of Science

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

July 2, 1999 -- Vol. 3 Number 27

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For the real amazement, if you wish to be amazed, is this
process: You start out as a single cell derived from the coupling
of a sperm and an egg; this divides in two, then four, then
eight, and so on, and at a certain stage there emerges a single
cell which has as all its progeny the human brain. The mere
existence of such a cell should be one of the great astonishments
of the Earth. People ought to be walking around all day, all
through their waking hours calling to each other in endless
wonderment, talking of nothing except that cell.
-- Lewis Thomas (1913-1993)

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Contents of This Issue:

1. On Biotechnology and Future World Food Production
2. On Complexity in Chemistry
3. Osmotic Pressure and Colloidal Interactions
4. On the Organization of Replication and Transcription
5. On the Molecular Basis of the Neurodegenerative Diseases
6. Myopia and Ambient Light at Night

In Focus: On the Art of Physics

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1. ON BIOTECHNOLOGY AND FUTURE WORLD FOOD PRODUCTION
The consumption of nutrients is one of the main activities of all
living systems, and the development and improvement of production
of nutrient sources ("food") has been one of the main activities
of the human species throughout its history. It is generally
believed that the application of new techniques in molecular
biology and genetics to agriculture will be of great importance
to our species in the next century, and indeed that application
is already underway and essentially constitutes the beginnings of
a revolution in the technology of nutrient production.
Technological revolutions, however, are hardly ever without
opponents, people made uneasy by the idea of change and the
possible risks of change. Indeed, the risks are sometimes severe,
involving social and economic upheavals in large populations.
These days, one focus of such opposition to change is the
introduction of new methods in agricultural technology,
particularly the application of genetic engineering techniques to
crop production. At the present time in human history, the prime
movers in applied science are in the commercial sector, profit-
making enterprises that essentially put up the capital required
for applied science in order to bring a return on the investment
to their shareholders. That is our current system, and in the
context of agricultural technology, it is to be expected that
those corporate enterprises responsible for the application of
genetic engineering to agriculture will bear the brunt of vocal
opposition generated by fears of technological innovation. One
corporate enterprise that has received a good deal of that brunt
is the Monsanto Company, a leader in the application of genetic
engineering in agriculture worldwide. Today, in the United
Kingdom, protesters wreck experimental crops designed to improve
food production; in 1815, in the same region, protesters wrecked
the new machines of the Industrial Revolution designed to improve
the production of cloth and other goods.
... ... G.M. Kishore and C. Shewmaker (Monsanto Company, US)
present a review of the application of biotechnology to improve
human nutrition in developing and developed regions of the world,
the authors making the following points:
     1) Since the beginning of this century, agriculture has
intensified with a) the discovery of economical chemical
processes to reduce nitrogen to ammonia and the use of
nitrogenous fertilizers; b) superior genetics with hybrid as well
as varietal crops; c) the discovery and use of chemical
pesticides to manage weeds, microbes, and insects.
     2) Over the past 50 years, society has faced the challenge
of feeding an ever-growing world population. Human population has
literally doubled in the last 40 years and increased 6-fold in
the last 200 years. The challenge over the next 50 years will be
to not only feed more people, but to do so in a manner which
takes into account probabilities such as the following:
... ... a) There will be less arable land. A combination of
overplowing, overgrazing, and deforestation has caused soil
erosion to exceed soil formation. Countries particularly hard hit
are those in continents like Africa, where soil is shallow to
begin with. The next generation of farmers in Africa will need to
feed not the 719 million people of today, but the 1.45 billion
people in the year 2025.
... ... b) There will be fewer resources, particularly
nonrenewable resources such as phosphorus and potassium, which
are used in fertilizers. While it can be argued that we have
sufficient natural deposits of these minerals to last another 200
years, technologies that minimize ore extraction and dispersion
over vast areas of land will enhance the sustainability of our
agricultural systems.
... ... c) There will be less water, and the quality of remaining
water will be reduced as demand increases. Water use has tripled
since mid-century, and water tables are falling around the world.
Seventy percent of all the water pumped from underground or drawn
from rivers is used for irrigation, and if we face a future of
water scarcity, we also face a future of food scarcity.
... ... d) Fewer people will engage in primary agriculture in
both developed and developing countries. In the US, less than 1
percent of the population is engaged in primary agriculture,
compared with 60 percent of the population in the early 1900s.
     3) Biotechnology is a discipline that has developed rapidly
during the last two decades. This technology is based on the
ability to introduce precise genetic changes into an organism.
Plant biotechnology, in particular, has evolved rapidly over the
course of the last 15 years. Every major crop can be subject to
precise genetic modifications based on our ability to introduce
and express genes in crops. Plant biotechnology, therefore,
should substantially augment plant breeding, which until now has
been based on the ability to harness genes into plants either by
sexual crossing or laboratory techniques such as cell fusion.
     4) Concerning the herbicide "Roundup" (a Monsanto product),
and the genetic engineering of crops that resist that herbicide
so the herbicide can be used to protect those same crops against 
weeds (it is such genetically engineered crops that have provoked
militant destructive protests in the UK), the authors present the
following details: "Roundup-Ready" soybeans (the genetically
engineered crop) contain a gene encoding the enzyme
5-enolpyruvylshikimate 3-phosphate synthase, an enzyme which is
involved in the biosynthesis of aromatic amino acids in plants.
The gene for this enzyme, when the gene is naturally present in
soybeans, produces a form of the enzyme sensitive to glyphosate,
the active ingredient of the herbicide Roundup. In genetically
engineered Roundup-Ready soybeans, the gene has been replaced by
a gene that encodes a catalytically active but glyphosate-
tolerant form of the same enzyme. Expression of the new gene in
plants renders in those plants adequate tolerance to the
herbicide, which can then be used to protect the plants from
weeds [*Note #1].
-----------
G.M. Kishore and C. Shewmaker: Biotechnology: Enhancing human
nutrition in developing and developed worlds.
(Proc. Natl. Acad. Sci. US 25 May 99 96:5968)
QY: Ganesh M. Kishore [ganesh.m.kishore@monsanto.com]
-----------
Text Notes:
... ... *Note #1: Editor's note: Such are the scientific elements
underlying the protest destruction of experimental and
demonstration crops in the UK and elsewhere. Given a hundred
years and a bit of luck, the same gene modification could perhaps
be achieved with the old technique of plant breeding. It is an
instructive irony that the same gene modification using the old
technique would probably not produce a single protest anywhere.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 2Jul99
-------------------
Related Background:
UK PROTESTERS DESTROY GENETICALLY ENGINEERED SUGAR BEET
A plot of genetically engineered sugar beet at an agricultural
show in eastern England (Royston) was destroyed by protesters.
The purpose of the sugar beet exhibit at the show was to
demonstrate the environmental benefits of using Monsanto's
"Roundup Ready" herbicide, which is said to encourage wildlife by
allowing weeds to grow longer and thus provide a source of food.
A spokesperson for the protest group "GenetiX Snowball" stated
the purpose of the destruction was to intimidate farmers against
growing genetically engineered crops. Four people participated in
the demonstration, and evidently no arrests were made. UK plant
breeders have stated UK farmers will achieve higher yields and
lower costs by using genetically modified crops. The US is
already marketing genetically engineered maize and soybeans and
plans to bring genetically engineered sugar beet onto the market
next year. (SW Bulletin 17 Jun 99)
-------------------
Related Background:
ELEVATING VITAMIN E CONTENT OF PLANTS VIA GENETIC ENGINEERING
The *chloroplasts of higher plants produce numerous compounds
important for human agriculture and nutrition. *Tocopherols, the
lipid-soluble *antioxidants sometimes known collectively as
vitamin E, are one such group of compounds and are synthesized
only by photosynthetic organisms. The 4 naturally occurring
tocopherols, alpha-, beta-, gamma-, and delta-tocopherol, differ
only in the number and position of methyl substituents on the
aromatic ring. In addition to their role as antioxidants,
tocopherols stabilize polyunsaturated fatty acids within *lipid
bilayers by protecting them from *lipoxygenase attack. Of
tocopherol species present in foods, alpha-tocopherol is the most
important to human health and has the highest vitamin E activity.
Although all tocopherols are absorbed equally during digestion,
only alpha-tocopherol is preferentially retained and distributed
throughout the body. Alpha-tocopherol is an essential component
of mammalian diets, and intakes in excess of the US recommended
daily allowances are apparently correlated with decreased
incidence of a number of degenerative human diseases. Plant oils,
the main dietary source of tocopherols, typically contain alpha-
tocopherol as a minor component, but with high levels of
biosynthetic precursor, gamma-tocopherol. ... ... D. Shintani and
D. DellaPenna now report the use of genetic engineering to clone
the final enzyme in alpha-tocopherol synthesis, gamma-tocopherol
methyltransferase. The authors report that *overexpression of
gamma-tocopherol methyltransferase in *Arabidopsis seeds shifted
oil composition in favor of alpha-tocopherol. The authors suggest
that similar increases in agricultural oil crops would increase
vitamin E levels in the average US diet.
-----------
D. Shintani and D. DellaPenna: Elevating the vitamin E content of
plants through metabolic engineering.
(Science 11 Dec 98 282:2098)
QY: Dean DellaPenna [della_d@med.unr.edu]
-----------
Text Notes:
... ... *chloroplasts: Chloroplasts are cell organelles involved
in photosynthesis, and are found in all photosynthetic plant
cells. The typical higher plant chloroplast is lens-shaped and
approximately 5 microns in diameter. The number per cell can vary
from 1 to over 100, depending on the organism. There is some
evidence that chloroplasts may have originated from
photosynthetic bacteria that became *endosymbiotic with plant
cells.
... ... *endosymbiotic: Endosymbiosis is an arrangement in which
one organism lives inside another organism, but the term is
usually restricted to arrangements of mutual benefit, thus not
including parasite-host relationships.
... ... *Tocopherols: "Tocopherol" is a generic term for di- and
trimethyltocols. Alpha-tocopherol is 5,7,8-trimethyltocol.
Although the tocopherols are sometimes known collectively as
"vitamin E", the usual referent for vitamin E is alpha-
tocopherol.
... ... *antioxidants: In general, an antioxidant is any
substance that opposes oxidation or inhibits reactions produced
by dioxygen or peroxides. An antioxidant is usually effective
because it can itself be more easily oxidized than the substance
protected. The term is often applied to substances that can trap
free radicals, thereby breaking a chain reaction that normally
leads to extensive biological damage.
... ... *lipid bilayers: Lipid bilayers are spontaneously
forming self-organizing bimolecular layers of certain molecules
(lipids) with long nonpolar chains terminated by a polar group. 
Such molecules are found in cell membranes, and also in soaps. A
variety of artificial lipid bilayer membrane systems can be
investigated in the laboratory. The cell membrane itself is
basically a lipid-bilayer structure.
... ... *lipoxygenase: In general, any member of a group of
enzymes that catalyze the oxidation of polyunsaturated fatty
acids to a particular corresponding hydroperoxide. Such enzymes
are found widely distributed in plants and animals (including
humans).
... ... *overexpression: In general, the term "expression" refers
to any gene activity, but particularly to activity that results
in the production of the specific protein encoded by the gene.
The expression of genes is closely regulated in the cell, so that
underexpression and overexpression are potential pathological
abnormalities of cell function. In the context of this report,
however, overexpression is genetically engineered in a plant to
produce a result of potential human benefit.
... ... *Arabidopsis: (Arabidopsis thaliana) (thale cress) A weed
of the mustard family with a small genome of 120 million base
pairs. Arabidopsis is now an important laboratory species, and it
is presently the model for physiological, biochemical, cell
biological, and developmental studies of over 250,000 plant
species. 
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 19Feb99
-------------------
Related Background:
AGRICULTURAL GENOMICS PROPOSED AS 3RD TECHNOLOGICAL REVOLUTION
In an editorial in the journal Science, Philip H. Abelson
proposes that the next great revolution after the Industrial
Revolution and the computer-based revolution is already underway
and is the genomics revolution, and that the greatest ultimate
global impact of genomics will arise from the manipulation of the
DNA of plants. In the future, the world will obtain most of its
food, fuel, fiber, chemical feedstocks, and some of its
pharmaceuticals from genetically altered vegetation and trees.
Major companies such as Dow Chemical, DuPont, Monsanto, and
Novartis are spending billions of dollars annually on genetic
engineering and on acquiring stakes in genome-oriented companies.
Humans today employ the capabilities of relatively few plants.
Abelson suggests the major challenge is to explore the
opportunities inherent in the hundreds of thousands of plant
species.
QY: P.H. Abelson [science_editors@aaas.org]
(Science 27 Mar 98) (Science-Week 17 Apr 98)
-------------------
Related Background:
GENETIC ENGINEERING OF DISEASE-RESISTANT RICE CROPS
Genetic engineering is the general term used for recombinant DNA
technology, a set of methods for introducing foreign DNA into a
host organism. It usually but not always involves gene cloning,
and there have been some spectacular successes in this field, for
example, the production of human insulin by genetically engin-
eered bacteria, the insulin then available as a therapy for human
diabetes. One of the most exciting areas for the application of
genetic engineering is agriculture, in particular food crops,
where there is considerable and reasonable hope that genetically
engineered food crops will be of great importance in increasing
agricultural productivity in underdeveloped countries. Pamela C.
Ronald (University of California Davis, US) reviews the recent
genetic engineering of disease-resistant rice crops, and suggests
genetic engineering will be useful for changing additional
aspects of rice and other grains, including cold tolerance and
drought resistance, and that ultimately breeders and farmers will
be able to choose from a repertoire of genetically engineered
clones to increase food production in places and under conditions
where it is badly needed.
QY: P. C. Ronald, Univ. Calif. Davis, Plant Biol., (916) 752-7094
(Scientific American November 1997) (Science-Week 31 Oct 97)
-------------------
Related Background:
IRISH ACTIVIST GROUP SABOTAGES GENETICALLY ENGINEERED CROP
In Ireland, an environmental activist group called the Gaelic
Earth Liberation Front has destroyed a one-acre research crop of
genetically engineered sugar beet. Under the auspices of the
Irish Government, the crop was grown by the US chemical company
Monsanto to develop a sugar beet variety resistant to a widely
used herbicide. The Gaelic Earth Liberation Front said in a
statement: "This was Ireland's first genetically engineered crop
and we hope it will be the last." But of course it will not be
the last, and one wonders if this is activism for the sake of
activism by people who know little about the environment and
even less about biology. Patricia McKenna, a politician who
represents Dublin in the European Parliament, praised the
destruction of the sugar beet crop, accusing Monsanto and the
Irish government of "playing games with the Irish environment".
And that underscores the non-triviality of these events. The neo-
Luddite rumblings that are becoming common these days are useful
to some people with political power, which means both the source
of the rumblings and the politicians who use the rumblings need
to be confronted by the scientific community. Ultimately it is
the larger community which must be persuaded one way or the
other; it is the attitude of the larger community that will
determine the fate of the neo-Luddite groups and the politicians
who use them. Concerning the science involved, what is obvious to
the scientific community is not always obvious to the community
at large, and one can only hope the scientific community will see
its responsibility to make its case to the larger community by
forceful and articulate dissemination of information. There is no
other apparent reasonable road.
(Nature 9 Oct 1997) (Science-Week 24 Oct 97)


2. ON COMPLEXITY IN CHEMISTRY
The term "complexity" is fashionable in science these days, the
interest presumed to indicate a movement away from reductionism,
away from the idea that the behavior of a system is best
understood in terms of how the components of the system behave
and interact. A focus on "complexity", however, is not perforce
anti-reductionist. Indeed, in practice, with real systems, the
behavior of a system is often not predictable from knowledge of
the behavior of its components, but most often this is simply
because that knowledge is incomplete, and not because of any
_principle_ barring prediction of the behavior of the system from
knowledge of its parts. Even systems exhibiting *chaotic
fluctuations are not necessarily non-reductionist, since such
systems are mathematically deterministic. In any case, faced with
an apparent unpredictability of a system given available
information about its parts, one looks for predictive global
methods to understand the system, methods that do not depend upon
a detailed knowledge of the behavior of the components of the
system. Thermodynamics is exactly such a global method of great
utility in chemistry and physics, and since thermodynamics is a
method of analysis that goes back to its originator Carnot in
1824, one can safely say that the idea of special methods to deal
with "complexity" is quite old. In our time, at least for ideal
systems, we can derive the equations of thermodynamics from
statistical mechanics, i.e., derive the global equations from
equations for the behavior of components. But Nicolas Sadi Carnot
(1796-1832) never heard of statistical mechanics, which was
introduced by Boltzmann (1844-1906) in 1871; Carnot founded
thermodynamics as a predictive global method to deal with an
important "complex" system of his time -- the steam engine.
... ... G.M. Whitesides and R.F. Ismagilov (Harvard University,
US) present a review of current ideas in chemistry concerning
"complexity", the authors making the following points:
     1) Chemistry has its own understandings of the term
"complexity". In one characterization, a complex system is one
whose evolution is very sensitive to initial conditions or to
small perturbations, one in which the number of independent
interacting components is large, or one in which there are
multiple pathways by which the system can evolve. Analytical
descriptions of such systems typically require nonlinear
differential equations. A second characterization is more
informal; that is, the system is "complicated" by some subjective
judgment and is not amenable to exact description, analytical or
otherwise.
     2) Faced with the impossibility of handling many real
systems exactly, chemists have evolved a series of approaches to
the treatment of complex systems. These treatments include
reasoning by analogy, averaging, linearization, drastic
approximation, pure empiricism, and detailed analytical solution.
The emphasis in thinking about complicated systems has been to
find methods that are predictive, even if they are non-
analytical. "Complexity" per se, the study of nonlinear processes
with high sensitivity to conditions, has not been the focus of
major effort.
     3) Chemistry has relied heavily on the ability of ensemble
properties that are obtained through thermodynamics and
statistical mechanics to make it unnecessary to consider the
behavior of individual molecules. However, single-molecule
chemistry is now making it possible to inquire about individual
molecular behaviors, and the behavior of macromolecules is a
promising area of research because of the existence of many
possible molecular conformations, each with different properties.
     4) At the core of chemical interest in complexity are the
two fundamental problems concerning life: a) how collections of
molecules give rise to the varieties of behaviors that
characterize cells and organisms; and 2) how individual molecules
might have originally assembled into collections that had the
characteristics of life (energy dissipation, self-replication,
and adaptation). Whether the understanding of complexity at the
molecular level will reveal important elements of the structure
of life is unclear.
     5) One of the opportunities in fundamental chemical research
is to learn from biology and to use what is learned to design
non-biological systems that dissipate energy, replicate, and
adapt. Whether such systems would model life is not critical;
they would unquestionably be interesting and probably important.
-----------
G.M. Whitesides and R.F. Ismagilov: Complexity in chemistry.
(Science 2 Apr 99 284:89)
QY: George M. Whitesides [gwhitesides@gmwgroup.harvard.edu]
-----------
Text Notes:
... ... *chaotic fluctuations: The term "chaotic", in this
context, is specific. In the study of physical systems, the
term "chaotic behavior" has a specific meaning: the behavior of a
system is said to be "chaotic" if its final state is so sensitive
to the system's precise initial conditions that the behavior of
the system is in effect unpredictable and cannot be distinguished
from a random process, even though the behavior of the system is
strictly determinate in a mathematical sense. In other words, a
deterministic system characterized by extremely sensitive
instabilities, despite the system being determinate, can exhibit
behavior that is unpredictable, and the system is then called
"chaotic". During the past several decades, the analysis of such
chaotic systems has intrigued both physicists and mathematicians.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 2Jul99


3. OSMOTIC PRESSURE AND COLLOIDAL INTERACTIONS
Osmosis is the passage of a solvent through a semipermeable
membrane separating two solutions of different concentrations. A
semipermeable membrane is one through which the molecules of a
solvent can pass but the molecules of most solutes cannot. There
is a thermodynamic tendency for solutions separated by such a
membrane to become equal in concentration, the water (or other
solvent) flowing from the weaker to the stronger solution [*Note
#1]. Osmosis will stop when the two solutions reach equal
concentrations, and can also be stopped by applying a pressure to
the liquid on the stronger solution side of the membrane. The
pressure required to stop the flow from a pure solvent into a
solution is a characteristic of the solution, and is called the
"osmotic pressure". Osmotic pressure depends only on the
concentration of particles in the solution, not on their nature
(i.e., it is a "colligative" property). Osmotic pressure is a
subtle ubiquitous phenomenon that is relevant at scales extending
from molecules to biological cells and tissues. For sufficiently
low concentrations, the osmotic pressure follows an "ideal gas"
law (van't Hoff Law): p = N/V x kT, where p is the osmotic
pressure, N/V is the number of particles per unit volume, k is
the Boltzmann constant, and T is the temperature. In polymer
physics, osmotic pressure measurements provide a useful method of
determining molecular weights. In biological systems, a proper
osmotic pressure balance is essential for the proper functioning
of cells and tissues; in fact, cells have apparently evolved
special mechanisms ("ion pumps") to regulate the osmotic pressure
build-up that results from the presence in the cytoplasm of cells
of a large concentration of proteins and other charged molecules
with their associated counterions. In theory, in a solution with
macromolecules present, two surfaces that come in close contact
(close enough to exclude the solute particles from the gap
between them) experience an attractive force ("osmotic depletion
interaction") caused by the osmotic pressure.
... ... M. Singh-Zocchi et al (3 authors at 2 installations, DK)
now report a measurement of the osmotic depletion interaction by
using a micron-sized glass sphere bound to a flat glass plate
through a single molecular attachment in an *albumin-containing
solution [*Note #2]. The technique involves the use of laser beam
scattering to follow the confined Brownian motion of the sphere
and determine the mean distance between the sphere and plate. The
total interaction potential is derived from this distance, and
the osmotic contribution is obtained by varying the solute
concentration. The authors report they obtain the osmotic part of
the interaction potential in experiments with a resolution of
sphere-wall distance less than 1 nanometer and a resolution of
total interaction potential less than 1 kT (room temperature).
The osmotic part of the attractive interaction has a range
related to the size of the albumin molecule-counterion entity
(which is experimentally manipulated by altering pH), and the
authors report the experimental results are in broad agreement
with the geometric model first proposed by Asakura and Oosawa
(1954).
-----------
M. Singh-Zocchi et al: Osmotic pressure contribution of albumin
to colloidal interactions.
(Proc. Natl. Acad. Sci. US 8 Jun 99 96:6711)
QY: Mukta Singh-Zocchi [missingh@nbi.dk]
-----------
Text Notes:
... ... *Note #1: From the standpoint of density gradients, the
essential considerations are as follows: A solution of particles
in a solvent, where the particles are unequally distributed,
contains two density gradients: one density gradient of particles
and one density gradient of solvent. If the system contains no
barrier to solute or solvent movement, both solute and solvent
are redistributed by Brownian motion with a resultant
equalization of their gradients. If the system contains a barrier
to solute movement but no barrier to solvent movement (e.g., a
semipermeable membrane), solvent movement will occur according to
the solvent density gradient. In real systems, the two gradients
are always interactive, since the solubility of a solute in a
solvent implies an interaction with that solvent.
... ... *albumin: The protein albumin has a special role in
regulating the osmotic pressure balance at the level of blood
vessels, since it is the largest protein constituent of blood
plasma and is present at a concentration of approximately 0.6
millimolar (approximately 40 milligrams/milliliter). An abnormal
deficiency of albumin can lead to water passing from the
bloodstream into the tissues (edema).
... ... *Note #2: In this experimental system, the glass sphere
is bound to the glass plate at a single point through a *biotin-
avidin-biotin connection (essentially a pivot). The surface of
the sphere and the surface of the plate are both covered with a
monolayer of albumin, and the solution contains the same albumin 
(bovine serum albumin). The experiment is conducted in a range of
pH in which the albumin is negatively charged. The experimental
system involves a large number of such attached spheres, but the
photodiode-optical apparatus measures the behavior of only a
single sphere as observed with a microscope.
... ... *biotin-avidin-biotin: Biotin (coenzyme R, vitamin H) is
cis-hexahydro-2-oxo-1H-thieno[3,4,-d]-imidazoline-4-valeric acid.
It is the D-isomer component of the vitamin B2 complex, and is a
small molecule with a high affinity for the glycoprotein *avidin.
... ... *avidin: Avidin is a glycoprotein obtained from egg white
with a high affinity for biotin. A number of reaction
amplification and visualization methods involve labelled avidin
binding to macromolecules tagged with biotin.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 2Jul99
-------------------
Related Background:
INTERACTION BETWEEN LIKE-CHARGED COLLOIDAL SPHERES
The interactions between *colloidal particles in electrolyte
solutions play an apparently central role in the *phase behavior
and agglomeration kinetics of colloidal dispersions. These
interactions are thus of fundamental importance for understanding
the properties of inorganic materials (e.g., ceramics composed of
nanoparticles), foods such as milk, and solutions of
biomacromolecules such as globular proteins. After decades of
theoretical and experimental efforts, the long-accepted theories
for describing the interactions of colloidal particles in
electrolyte solutions have been challenged by results from recent
experiments. Included in this challenge is the issue of apparent
attractive electrostatic forces between like-charged colloidal
particles in an electrolyte solution. ... ... J. Wu et al
(University of California Berkeley, US) now report *Monte Carlo
simulation studies that indicate the existence of a short-range
attractive force between identical macroions in electrolyte
solutions containing divalent counterions. The authors report
strong evidence (complementing recent and related results by
others) of attraction between a pair of spherical macroions in
the presence of added salt ions for the conditions where the
interacting macroion pair is not affected by any other macroions
that may be in the solution. The authors state that classical
theories fail to describe the attractive interactions found in
their simulations, with one set of classical theories (Derjaguin-
Landau-Verwey-Overbeek) predicting only repulsive interactions
and another set of theories (Sogami-Ise) predicting a long-range
attraction that is too weak and that occurs at too large macroion
separations. The authors suggest their simulations provide
fundamental "data" for an improved theory of colloidal
interactions in electrolyte solutions.
-----------
J. Wu et al: Interaction between like-charged colloidal spheres
in electrolyte solutions.
(Proc. Natl. Acad. Sci. US 22 Dec 98 95:15169)
QY: John M. Prausnitz [lindar@cchem.berkeley.edu]
-----------
Text Notes:
... ... *colloidal particles: In general, a colloid is a system
of particles 1 to 1000 nanometers in diameter dispersed in
another phase.
... ... *phase behavior: In this context, the term "phase" refers
to any part of a system which is uniform in chemical composition
and physical properties and separated from other homogeneous
parts of the system by boundary surfaces. Also in this context,
the term "phase behavior" refers to the equilibrium relationships
between water, the dispersed colloid, and dissolved non-colloidal
electrolytes.
... ... *Monte Carlo simulation studies: In general, a "Monte
Carlo method" is any method for obtaining a statistical estimate
of a desired quantity by random sampling. In the most successful
applications, the desired quantity is a statistical parameter,
and the sampling is made from an artificial population that may
be a model of the physical system itself. The method is of
considerable utility in handling certain intractable applied
mathematical problems.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 5Mar99
-------------------
Related Background:
ATTRACTION BETWEEN LIKE-CHARGED SPHERES IN A CHARGED PORE
A colloid is a system of particles 1 to 1000 nanometers in
diameter dispersed in another phase, and such systems, 
particularly systems of electrically charged colloids, have
important practical significance and are also of considerable
theoretical interest. The existence of long-range attractive (as
opposed to the expected repulsive) electrostatic forces between
particles of like charge is one of the current major
controversies of colloid science. The established classical
theory (Derjaguin-Landau-Vervey-Overbeek) of colloidal
interactions predicts that an isolated pair of like-charged
colloidal spheres in an electrolyte should experience a purely
repulsive *screened electrostatic (coulombic) interaction. Direct
measurements of such interactions have shown quantitative
agreement with the classical theory, but recent experiments have
provided evidence that the effective interparticle potential can
have a long-range attractive component in more concentrated
suspensions and for particles confined by charged glass walls.
This long range attraction in concentrated systems is apparently
due to multi-body interactions. Theoretical explanations have
been proposed but remain the subject of controversy.
... ... Bowen and Sharif (University of Wales, UK) now present a
quantitative theoretical explanation of the attractive forces
between confined colloidal particles, the theory based on direct
solutions of the classical nonlinear Poisson-Boltzmann equation
for two like-charged spheres confined in a cylindrical charged
pore. The calculations show that the attraction may be explained
by the redistribution of the electric double layer of ions and
counterions in solution around the spheres, owing to the presence
of the wall. The authors suggest there is thus no need to revise
the established concepts of underlying theories of colloidal
interactions. [Editor's Note: The theoretical result in this
paper is unequivocal: the calculation shows that for the given
boundary conditions, the force between two particles of like
charge dips below zero (i.e., becomes attractive) before
returning to zero at infinite distance.]
QY: W. Richard Bowen (r.bowen@swansea.ac.uk)
(Nature 18 Jun 98 393:663) (Science-Week 3 Jul 98)
... ... *screened: Screening is a reduction of the effective
electric field at a point, the reduction due to the space charge
of ambient charged particles of sign opposite to the source of
the field.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 3Jul98


4. ON THE ORGANIZATION OF REPLICATION AND TRANSCRIPTION
In the study of living organisms, the term "replication" refers
in general to the duplication of the organism and in particular
to the duplication of the genome of the organism, a genome that
except in certain viruses consists of DNA. In the particular
sense, therefore, replication refers to duplication of the DNA
molecule. The term "transcription" refers to the process by which
genetic information in DNA is converted into RNA, i.e., the
production of an RNA molecule from a DNA molecule template. Both
processes, replication and transcription, involve the activity of
specific polymerization catalysts (enzymes) called "polymerases".
DNA polymerases catalyze the formation of DNA polymers, either
from DNA templates, or in certain special viruses, from RNA
templates; and RNA polymerases catalyze the formation of RNA
polymers from DNA templates. One general question that
immediately arises is whether these polymerases are mobile or
fixed: in other words, does the polymerase track along the
template, or is the polymerase relatively fixed and the template
pulled into the polymerase entity for the reading of the
sequence? ... ... Peter R. Cook (University of Oxford, UK)
presents an extensive review of current research concerning the
organization of replication and transcription, the author making
the following points:
     1) Models for replication and transcription often display
polymerases that track like locomotives along their DNA
templates. However, recent evidence supports an alternative model
in which DNA and RNA polymerases are immobilized by attachment to
larger structures, where they reel in their templates and extrude
newly made nucleic acids. These polymerases apparently do not act
independently, but they are concentrated in discrete "factories",
where they work together on many different templates.
     2) The evidence for DNA polymerases being fixed is indirect
and of four general types: a) theoretical evidence suggests how
attached DNA polymerases might be coordinately controlled; b)
some activities are immobilized during reactions in vitro; c)
active DNA polymerases and nascent DNA resist detachment from the
cell substructure; d) newly made DNA is concentrated in discrete
foci, implying that the polymerases are not free to track. The
same evidence supports the idea that active polymerases are
grouped together. As a result, many researchers now accept that
DNA polymerases are fixed in factories which are assembled and
disassembled during various phases of the *cell cycle.
     3) The idea that RNA polymerases are fixed is less widely
accepted, but the evidence is of the same four types listed
above, and the author suggests that RNA polymerases are also
fixed.
     4) The author suggests that life forms concentrate molecules
so that those molecules can react together, and that by
extension, it might be expected that the polymerases responsible
for the vital processes of replication and transcription would be
concentrated within the cell in specific locations.
-----------
Peter R. Cook: The organization of replication and transcription.
(Science 11 Jun 99 284:1790)
QY: Peter R. Cook [Peter.Cook@Path.OX.AC.UK]
-----------
Text Notes:
... ... *cell cycle: The term "cell cycle" refers to the ordered
sequence of phases through which a cell passes from one mitotic
(i.e., replicating) cell division to the next.
-------------------
Related Background:
EVIDENCE FOR A FACTORY MODEL OF DNA REPLICATION
For all organisms, the production of viable progeny depends on
the faithful replication of DNA by the enzyme DNA polymerase,
which incorporates nucleoside triphosphates into a DNA chain.
This enzyme is actually a multi-enzyme complex that takes
different forms in *prokaryotes and *eukaryotes. Two general
models have been proposed for DNA replication. In one model, DNA
polymerase moves along the template DNA (like a train on a
track); in the other model, the polymerase is stationary (like a
factory), and the template DNA is pulled through.
... ... K.P. Lemon and A.D. Grossman present the results of a
study to distinguish between the two models. The authors report
they visualized DNA polymerase of the bacterium *Bacillus
subtilis in living cells by the creation of a *fusion protein
containing the DNA polymerase catalytic subunit (PolC) and green
fluorescent protein (GFP). The authors report the PolC-GFP entity
was found localized at discrete intracellular positions,
predominantly at or near mid-cell, rather than being distributed
randomly. The authors propose their results suggest that the
polymerase is anchored in place, thus supporting the model in
which the DNA template moves through polymerase.
-----------
K.P. Lemon and A.D. Grossman (Mass. Inst. of Technol., US)
Localization of bacterial DNA polymerase: Evidence for a factory
model of replication.
(Science 20 Nov 98 282:1516)
QY: Alan D. Grossman 
-----------
Text Notes:
... ... *prokaryotes: In general, cells without a cell nucleus
and other membrane-bound organelles.
... ... *eukaryotes: In general, cells with a cell nucleus and
other membrane-bound organelles.
... ... *Bacillus subtilis: The genus Bacillus is a group of
free-living rod-shaped bacteria, some species of which produce
antibiotics. The genome of B. subtilis has been completely
sequenced.
... ... *fusion protein: In this context, a "fusion protein" is a
protein that results from the fusion of two genes. The essential
idea here is the fusion of the gene for DNA polymerase with the
gene for the green fluorescent protein, so that when and where
the new DNA polymerase-fluorescent protein is expressed it can be
located by its fluorescent moiety. (See below for a related use
of the technique.)
-------------------
Summary & Notes by SCIENCE-WEEK  25Dec98
-------------------
Related Background:
NEW FUSION PROTEIN ENABLES VISUALIZATION OF DNA IN LIVE CELLS
Eukaryotic cells are cells having membrane bound organelles such
as a nucleus, and the term "histones" refers to a group of 8
small basic (as opposed to acidic) proteins found in combination
with nucleic acids in eukaryotic chromosomes. The histone-nucleic
acid complexes are essential aspects of chromosome molecular
architecture. ... ... A class of DNA-histone assemblies typical
of many cancer cells called "double minute chromosomes" have
until now been difficult to visualize because of their small
size. Now a group at the Salk Institute (US) has developed a
working method involving a fluorescent fusion protein. The method
involves fusing a human histone gene to the gene for a green
fluorescent jellyfish protein, with the combined new gene
expressed in a human cell line.
QY: T. Kanda, Salk Institute, 10010 N. Torrey Pines Road, La
Jolla, CA 92037 US.
(Curr. Biol. 8:377 1998) (Science-Week 27 Mar 98)
-------------------
Related Background:
MOLECULAR BIOLOGY: AN INTEGRATED TRANSCRIPTION COMPLEX MODEL
In molecular biology, transcription is the process by which
genetic information in DNA is converted into RNA. The central
event in transcription is the *RNA-polymerase-catalyzed
conversion of the sequence code of the template strand of a gene
into a complementary RNA transcript. This RNA may in turn be
translated into a protein, or the RNA may instead serve a
structural or regulatory role, or the RNA may form the genome of
an *RNA virus. Formation of an RNA transcript has traditionally
been divided into 3 sequential stages, called *initiation,
*elongation, and *termination, and all are subject to regulatory
control. ... ... In a review of transcription, Peter H. von
Hippel (University of Oregon, US) presents what is termed "an
integrated model of the transcription complex", and the author
makes the following points: 1) Recent findings now allow the
development of an integrated model of the thermodynamic, kinetic,
and structural properties of the transcription complex in the
elongation, termination, and editing phases of transcript
formation. 2) Concerning the 3 traditional sequential stages, it
may now be more appropriate to divide the overall process into
two major phases: a) activation and transcript initiation, and b)
transcript elongation, with the latter including termination
(transcript release) and editing (transcript shortening and
resynthesis with increased fidelity. 3) The author suggests the
new model provides an operational framework for placing known
facts and can be extended and modified to incorporate new
advances. 4) The most complete information about transcriptional
mechanisms and their control continues to come from the bacterium
Escherichia coli system, upon which most of the explicit
descriptions in the author's model are based. The transcription
machinery of higher organisms, despite its greater inherent
complexity, appears to use many of the same general principles,
and thus the lessons of E. coli continue to be relevant. In
conclusion, the author points out the following problems in
current research in this area: 1) We do not yet know the
molecular structure of any multi-subunit RNA polymerase. 2) We do
not know the exact path taken through the polymerase by the DNA
and RNA framework of the transcription complex. 3) We do not know
how various *transcription factors change the rates of movement
or the stability properties of the transcription complex. 3) We
do not know how these changes are further modulated by the local
sequences of the template and non-template DNA and the nascent
transcript.
QY: Peter H. von Hippel 
(Science 31 Jul 98 281:660) (Science-Week 28 Aug 98)
-------------------
Related Background:
... ... *RNA polymerase: RNA polymerase is an enzyme that
polymerizes ribonucleoside triphosphates into RNA in the order
dictated by a DNA or RNA template. RNA polymerases are found in
all living cells, with one type found in prokaryotes (cells
without a cell nucleus and other membrane-bound organelles), and
3 types found in eukaryotes (cells with a cell nucleus).
... ... *RNA virus: Viruses either have an RNA genome or a DNA
genome, with the respective nucleic acid core single stranded or
double stranded, depending on the viral species. In general, RNA
viruses are subdivided into 3 types, depending on the details of
the virus-host cell viral replication process.
... ... *initiation: In this context, this is the stage that
begins when RNA polymerase binds to the double-stranded DNA
molecule and incorporates the first nucleotide(s).
... ... *elongation: In this context, the phase during which the
RNA polymerase moves along the DNA template and extends the
growing RNA chain by adding one nucleotide at a time.
... ... *termination: In this context, the stage in which RNA
synthesis ends and the RNA polymerase complex disassembles from
the transcription unit.
... ... *transcription factors: Regulatory proteins that
determine the efficiency with which RNA polymerases bind to DNA
promoter regions during transcription. A "promoter" is a type of
control element, approximately 100 bases long, found in the
genome associated with various genes.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 28Aug99
-------------------
Related Background:
STRUCTURAL ANALYSIS OF DNA-POLYMERASE ACTIVITY
DNA polymerases, of which there are several types, are enzymes
that specifically assemble deoxyribonucleoside triphosphates (DNA
nucleotides) into DNA strands in the order dictated by a temp-
late. In addition to the template, a fragment of RNA or DNA must
be annealed to the template as a primer, the catalyzed polymer
synthesis then consisting of additions to one end of that primer.
A critical aspect of DNA polymerase activity is that the template
is copied with high fidelity, but the precise mechanism by which
nucleotides are in sequence correctly incorporated in the copy is
not yet known. ... ... Kiefer et al (4 authors at 2 installat-
ions, US) report high resolution crystal structures (1.8 ang-
stroms) of a thermostable bacterial (Bacillus stearothermophilus)
DNA polymerase (type I) fragment, the fragment bound with DNA
primer templates at the active polymerase site, and the complex
retaining catalytic activity and allowing direct observation of
the products of several rounds of nucleotide incorporation. The
polymerase also retains its ability to discriminate between
correctly and incorrectly paired nucleotides in the crystal. The
authors suggest their procedure makes possible snapshots of
successive polymerase complexes, and that the structures provide
the most detailed view of any polymerase DNA complexes yet
determined.
QY: Lorena S. Beese 
(Nature 15 Jan 98) (Science-Week 30 Jan 98)
-------------------
Related Background:
MECHANISM OF RNA POLYMERASE NUCLEOSOME TRANSCRIPTION
... RNA polymerase type III is specific to transfer RNA (tRNA)
and ribosomal RNA (rRNA). Transfer RNA is a class of small RNA
molecules that transfer individual amino acids to a growing
polypeptide chain during protein synthesis, and ribosomal RNA is
a class of RNA molecules that have an important role in the
structure of ribosomes, the large molecular entities that carry
out protein synthesis in all cells. All the RNA polymerases are
large and complex molecules with molecular weights of approx-
imately 500,000 daltons. Nucleosomes are higher order structures
of eukaryotic chromosomal DNA, the structures composed of coils
of the DNA double helix around a complex of 8 small basic
proteins called histones. Studitsky et al (4 authors at 2 instal-
lations, US) report that the large yeast RNA polymerase III
transcribes through a single nucleosome, with direct internal
nucleosome transfer in which histones never leave the DNA
template. The authors suggest their results show that a eukary-
otic polymerase is capable of transcribing through a nucleosome
without displacing it from the template, and that this ability
may reflect a property of importance for the transcription
process in vivo.
QY: Gary Felsenfeld, US Nat. Inst. of Health, Bethesda, MD
20892-0148.
(Science 12 Dec 97) (Science-Week 2 Jan 98)


5. ON THE MOLECULAR BASIS OF THE NEURODEGENERATIVE DISEASES
The term "neurodegenerative disorders" is loosely applied to a
group of chronic and progressive diseases of the nervous system,
all of which are characterized by selective and symmetric loss of
neurons in motor, sensory, or cognitive systems. Some
neurodegenerative diseases are extremely cell-specific, causing
loss of only one type of nerve cell, while the neuronal loss
caused by other neurodegenerative diseases is more general,
affecting a wide variety of nerve cells. In all cases, these
diseases primarily affect nerve cells and not other cells.
... ... Joseph B. Martin (Harvard University, US) presents a
review of the molecular basis of neurodegenerative disorders, the
author making the following points:
     1) Delineation of the patterns of cell loss and
identification of disease-specific cellular markers have aided in
the classification of these diseases. For example:
... ... a) *Alzheimer's disease is characterized by *senile
plaques, *neurofibrillary tangles, neuronal loss, and
*acetylcholine deficiency.
... ... b) *Parkinson's disease is characterized by *Lewy bodies
and depletion of *dopamine.
... ... c) *Amyotrophic lateral sclerosis is characterized by
*cellular inclusions and swollen *motor axons.
... ... d) *Huntington's disease is characterized by loss of
*gamma-aminobutyric acid-containing neurons of the *neostriatum.
     2) *Mendelian inheritance can be demonstrated in many
neurodegenerative disorders. In some diseases, such as
Huntington's disease, a family history of the disease can be
ascertained in almost every case, whereas in other diseases, such
as Alzheimer's disease, Parkinson's disease, and amyotrophic
lateral sclerosis, about 1 to 10 percent of cases are inherited.
In other conditions, such as *spinocerebellar ataxia, the
syndromes have been difficult to classify because of clinical
overlap, and variants can only be differentiated by genotyping
after the mutant genes have been identified.
     3) In families with the above and other neurodegenerative
disorders, *linkage analysis, *positional cloning, and searches
for mutations in candidate genes have been extremely productive.
These efforts, which began in the 1980s with the search for the
gene that causes Huntington's disease, have led to the
identification of mutant genes in more than 50 disorders of the
nervous system.
     4) The genetic anomalies that cause neurodegenerative
diseases are varied and complex. In some diseases, several genes
have been found, each of which leads to a similar clinical and
pathological syndrome, with only variations in the age at onset
and the rate of progression to suggest that there are differences
in pathogenic mechanisms. In other disorders, errors in DNA
replication resulting in an increased number of *nucleotide
triplet repeats are associated with selective patterns of
neurodegeneration.
     5) In general, the various pathologies of the
neurodegenerative disorders apparently involve abnormalities in
the transport, degradation, and aggregation of proteins that lead
to cell-specific changes and ultimately to neuronal death,
probably by *apoptosis.
-----------
Joseph B. Martin: Molecular basis of the neurodegenerative
diseases.
(New England J. Med. 24 Jun 99 340:1970)
QY: Joseph B. Martin [joseph_martin@hms.harvard.edu]
-----------
Text Notes:
... ... *Alzheimer's disease: Alzheimer's disease is
characterized by the presence of large numbers of extracellular
agglomerations (plaques) and intracellular *neurofibril tangles
in the cerebral cortex of the brain. There is also a massive
neuronal cell loss. While plaques and tangles are found in normal
aging brains, they are more numerous and widespread in
Alzheimer's disease. The major protein component of the plaques
is a 39 to 43 amino acid peptide called beta-amyloid, which is
now known to be derived from a much larger protein called the
amyloid precursor protein. This latter protein has been found to
be expressed in every tissue studied.
... ... *neurofibril: A filamentous structure seen with the light
microscope and composed of ultramicroscopic tubular and
filamentous protein arrays (neurotubules and microfilaments). The
function of these structures is unknown.
... ... *senile plaques: In general, the term "plaque" refers to
a deposit. In this context, the deposits are usually
extracellular protein agglomerations.
... ... *neurofibrillary tangles: A neurofibril is a filamentous
structure seen with the light microscope and composed of
ultramicroscopic tubular and filamentous protein arrays
(neurotubules and microfilaments). The function of these
structures is unknown.
... ... *acetylcholine: In general, a neuron has input extensions
(dendrites) and a single but usually branched output extension
(axon). The junction between the terminal of a neuron's axon and
another neuron is called a "synapse". When studying the synapse,
the first neuron is called the "presynaptic" neuron, and the
second neuron is called the "postsynaptic" neuron.
Neurotransmitters are chemical substances released at the
terminals of nerve axons in response to the propagation of an
impulse to the end of that axon. The neurotransmitter substance
diffuses into the synapse, the junction between the presynaptic
nerve ending and the postsynaptic neuron, and at the membrane of
the postsynaptic neuron the transmitter substance interacts with
a receptor. Depending on the type of receptor, the result may be
an excitatory or an inhibitory effect on the postsynaptic nerve
cell. At present acetylcholine, 5 amines, 4 amino acids, 2
purines, and more than 28 peptides are known to be
neurotransmitters.
... ... *Parkinson's disease: A neurological disorder first
described by James Parkinson (1817) and associated with
degeneration of a specific small region of the brain and a
resultant loss of projection to several important brain centers.
... ... *Lewy bodies: Intracytoplasmic neuron inclusions
especially seen in Parkinson's disease.
... ... *dopamine: Dopamine is a neurotransmitter found in
several major areas of the brain, and the degeneration of
so-called dopamine neurons is apparently involved in Parkinson's
disease. Dopamine has also been implicated in the intricate
effects of the psychostimulating drugs associated with drug
abuse. The dietary precursors of dopamine are phenylalanine and
l-tyrosine.
... ... *Amyotrophic lateral sclerosis: A progressive disease of
motor neurons (spinal cord nerve cells that control voluntary
muscles). 50 percent of patients die within 3 years of the first
symptoms.
... ... *cellular inclusions: A general term for residual
entities in cytoplasm produced by metabolism; in this context,
granules or crystals not found in normal cells.
... ... *motor axons: Axons of motor neurons. They can be quite
long: a spinal cord motor neuron controlling muscles in a toe,
for example, has a cell body in the spinal cord and an axon that
runs as a single extension from the spinal cord down to the toe
musculature. Such axons usually propagate impulses at high
velocity (e.g., 100 meters per second).
... ... *Huntington's disease: (Huntington's chorea) First
described by George Huntington (1850-1916), the disease attacks
specific regions of the brain (e.g., caudate nucleus and
putamen), and leads to insanity and eventual death.
... ... *gamma-aminobutyric acid: A widely distributed brain
neurotransmitter.
... ... *neostriatum: This is a term used when considering the
two brain regions, the caudate nucleus and the putamen, as a
single anatomical entity.
... ... *Mendelian inheritance: In general, any inheritance
scenario following the classical Mendelian laws governing the
inheritance of chromosomal genes via the transmission of
chromosomes to subsequent generations, and producing inheritance
of single-chromosome-locus traits.
... ... *spinocerebellar ataxia: In general, an ataxia is an
inability to coordinate muscle activity during voluntary
movement. Spinocerebellar ataxia is the most common hereditary
ataxia. The spinocerebellar degenerative disorders are a group of
diseases involving neurons in several nervous system structures,
including the spinal cord and cerebellum.
... ... *linkage analysis: In general, an analysis of chromosomal
gene location based upon inheritance patterns.
... ... *positional cloning: In general, the identification of a
gene responsible for a disease from a knowledge of its position
in the human genome, and no assumptions about the gene product.
Inherited disease genes identified by positional cloning include
Duchenne muscular dystrophy and Huntington's disease.
... ... *nucleotide triplet repeats: (coding triplet repeats;
codon repeats) In general, a codon is the basic genetic
coding unit, a triplet of nucleotides in DNA. A codon repeat is a
string of identical codons which if expressed produce a string of
identical amino acids in a protein.
... ... *apoptosis: In general, programmed cell death produced by
control mechanisms designed to destroy defective cells.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 2Jul99


6. MYOPIA AND AMBIENT LIGHT AT NIGHT
Myopia (short-sightedness) occurs when the image of distant
objects, focused by the cornea and lens, falls in front of the
retina. It apparently usually arises from excessive postnatal eye
growth, particularly in the vitreous cavity (the interior of the
eyeball behind the lens). The prevalence of myopia is evidently
increasing, and now reaches 70 to 90 percent in some Asian
populations. In addition to requiring optical correction, myopia
is a leading risk factor for acquired blindness in adults because
it predisposes individuals to *retinal detachment, retinal
degeneration, and *glaucoma. Myopia typically develops in the
early school years, but it can appear in early adulthood. The
etiology of myopia is poorly understood, but may involve genetic
and environmental factors, such as viewing close objects,
although how this stimulates eye growth is not known. Research in
species as diverse as chicks and monkeys indicates that postnatal
eye growth and *refractive development are governed by a vision-
dependent retinal mechanism acting mainly within the eye, with
only limited participation of the brain and extra-ocular neural
pathways. The duration of the daily light period has been shown
to affect eye growth in chicks. ... ... G.E. Quinn et al (4
authors at University of Pennsylvania, US) now report a study of
the effects of light exposure on vision in 479 children. The
authors report a strong association between myopia and night-time
ambient light exposure during sleep in children before they reach
two years of age. The authors suggest that the statistical
strength of the association of night-time light exposure and
childhood myopia indicates that the absence of a daily period of
darkness during early childhood is a potential precipitating
factor in the development of myopia, and that it seems prudent
that infants and young children sleep at night without artificial
lighting in the bedroom, while these findings are evaluated more
comprehensively.
-----------
G.E. Quinn et al: Myopia and ambient lighting at night.
(Nature 13 May 99 399:113)
QY: Richard A. Stone [stone2@mail.med.upenn.edu]
-----------
Text Notes:
... ... *retinal detachment: The retina, consisting of 10 layers,
is a fragile neural-tissue membrane that receives images of outer
objects and transmits signals via the optic nerve to the brain.
"Retinal detachment" is a division of the retina from the
covering in the back of the eye (the choroid), the division most
often resulting from a hole in the retina that allows the fluid
of the vitreous cavity ("vitreous humor") to leak between the
retina and the choroid. Unless repaired early, a detached retina
results in irreversible blindness.
... ... *glaucoma: In general, an abnormal condition of high
fluid pressure within an eye. If untreated, acute glaucoma causes
complete and permanent blindness within 2 to 5 days. The symptoms
of chronic glaucoma develop over a period of years. Both acute
and chronic forms are treatable with drugs.
... ... *refractive development: In this context, the term
"refractive development" refers to the development of the
focusing mechanisms of the eye.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 2Jul99


=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-= 

IN FOCUS: ON THE ART OF PHYSICS
"One of the most trying aspects of practicing the art of physics
is that the shape of the answer is not known from the outset.
Although they can draw upon advanced experimental technology and
the wealth of data collected by past scientists, physicists must
work in the dark whenever they proceed close to the frontiers of
knowledge; they are aided only by a set of aesthetic prejudices,
a few mathematical tools, and the knowledge that whatever they
come across is unlikely to contradict directly the conclusions of
the past, although it may modify them. The ideas of theoreticians
must be at least somewhat amenable to being tested by others in
the community; experimenters need to make it seem plausible that
others could reproduce their work and achieve the same results.
But these guidelines leave more than enough room for error, and
the scientists who make the most remarkable advances -- perhaps
especially the most remarkable advances -- are almost inevitably
haunted by doubt, anxiety, and the fear of being forgotten.
Consider Werner Heisenberg, residing temporarily at Gottingen,
writing to his close friend Wolfgang Pauli... Here is how he
[Heisenberg] feels just after completing the work for which he
was later awarded the Nobel Prize: 'I've taken a lot of trouble
to make the work physical, and I'm relatively content with it.
But I'm still pretty unhappy with the theory as a whole... I
don't know whether I'm just too stupid to understand the
mathematics.'"

-- R.P. Crease and C.C. Mann: _The Second Creation_
   (Macmillan Publishing, New York 1986, p.52)


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The first issue of SCIENCE-WEEK appeared May 1, 1997, and it has
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Copyright (c) 1997-1999 SCIENCE-WEEK/Spectrum Press Inc.
All Rights Reserved

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