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ScienceWeek
SCIENCE-WEEK
A Weekly Email Digest of the News of Science
A journal devoted to the improvement of communication
between the scientific disciplines, and between scientists,
science educators, and science policy-makers.
July 6, 2001 -- Vol. 5 Number 27
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What they don't fathom is the burning, this obsessive
need for understanding. Why would anyone want to spend
their life in the clutter and stink of a laboratory?
Is there any money in it? they ask. How do you tell
them about the burning?
-- Anonymous
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Section 1
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Contents of this Issue (Full reports in Section 2):
1. IN BRIEF:
Fluid transitions in small volumes... Gravity waves and spin
rates in neutron stars... Women in physics faculties... Young
stars near the Solar System... Racial disparities in heart attack
treatment... Blood lead levels in young children... A new minute
early mammal... Cancer as an evolutionary process.
2. ASTROPHYSICS: ON X-RAY POLARIMETRY OF ASTRONOMICAL OBJECTS
X-ray astronomy has revealed some of the most violent and compact
spots in the Universe, such as the surfaces of pulsars, the close
orbits around giant black holes, and the blast waves of supernova
explosions. A new x-ray polarimeter promises to revolutionize
space-based observations.
3. STATISTICAL PHYSICS: ON AGGREGATION
A modification of Smoluchowski's classic theory of surface
aggregation provides a convenient opportunity to compare theory
and experiment in research on nucleation and growth of vapor-
deposited material on single crystal surfaces.
4. BIOCHEMISTRY: ON THE STRUCTURE OF A PROTEIN BARREL
The so-called "complexity" of proteins is based on our lack of
knowledge of the principles that relate component parts to global
function. A new detailed study of mutagenic amino-acid
substitutions in a specific enzyme suggests that a widely
occurring and important protein barrel conformation could be
encoded with a simplified amino-acid alphabet.
5. MEDICAL BIOLOGY:
MIDLIFE REDUCED ACTIVITY IN ALZHEIMER'S DISEASE
Patients with Alzheimer's disease are less active in early and
middle adulthood in terms of intellectual, passive, and physical
activities than members of a control group. Researchers suggest
that low participation in activities in midlife (in addition to
low levels of educational and occupational achievement) is a risk
factor for the disease.
6. MEDICAL BIOLOGY: TULAREMIA AS A BIOLOGICAL WEAPON
The causative agent of tularemia, F. tularensis, is one of the
most infectious pathogenic bacteria known, requiring inoculation
or inhalation of as few as 10 organisms to cause disease. An
aerosol dispersal of 50 kilograms of virulent F. tularensis over
a metropolitan area with 5 million inhabitants would result in
250,000 incapacitating casualties, including 19,000 deaths.
7. IN FOCUS: ON CHIMPANZEES
Many people misread evolution's signature easily and often.
Chimpanzees are not evolutionary challenged people, and people
did not evolve from gorillas. While they may look like hirsute,
sloped-foreheaded, primitive humans, chimpanzees evolved for some
5 million years after their ancestors diverged from our own.
8. FROM THE SCIENCEWEEK ARCHIVE: ON GENES AND BEHAVIOR
The question of genetic vs. non-genetic determinants of behavior
is an area of controversy in several branches of science, and
discussion of the question is on occasion contentious. Here is a
collection of reports on genes and behavior in humans, rats, and
insects, with some remarks on the controversy that may be
unexpected.
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Section 2
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1. IN BRIEF:
... ... PHYSICAL CHEMISTRY: In small volumes, fluids can assume
new properties important in biological interactions, fracture
propagation, and molecular adhesion. Experiments on a thin film
of cyclohexane confined within attoliter volumes reveal that
cyclohexane undergoes a drastic transition from a 3-dimensional
bulk fluid to a 2-dimensional adsorbate with strikingly different
properties and long-range density fluctuations of unexpected
magnitude. (Science 2001 292:905)
... ... ASTROPHYSICS: A neutron star resembles a gigantic atomic
nucleus, packing more than a solar-mass of neutrons inside a ball
only 20 kilometers in diameter. Theory suggests that neutron
stars should be born rotating rapidly, but in reality they spin
more slowly. New theoretical calculations suggest that neutron
stars may be slowed by the emission of gravity waves.
(Nature 2001 411: 31) (Phys. Rev. Lett. 2001 86:1148)
... ... PHYSICS FACULTIES: Despite the rise in the total number
of new physics faculty in the US, the fraction of jobs going to
women has fallen. Only 14 percent of academic physicists hired in
2000 were women, down from 17 percent in 1998. In contrast, there
was an increase in the number of new physics faculty that earned
their PhDs outside the US -- such faculty now make up more than a
third of new full-time physics faculty in US PhD-granting
departments. (Physics Today 2001 May)
... ... ASTRONOMY: A new perspective has formed among astronomers
on the history and contents of our corner of the Galaxy. Recent
data collected by various satellites suggest that our Solar
System is immersed in a spray of young stars from distant star-
forming regions. A very active star-formation complex is in the
general direction of the Scorpio and Centaurus constellations
(Sco-Cen region), and the data indicate vigorous star formation
in this region for perhaps the past 100 million years.
(Nature 2001 411:145)
... ... PUBLIC HEALTH: Several studies have reported that black
patients are less likely than white patients to undergo cardiac
catheterization after acute myocardial infarction. New evidence
indicates that racial differences in the use of cardiac
catheterization are similar among patients treated by white
physicians and those treated by black physicians, suggesting that
this pattern of care is independent of the race of the physician.
(New England J. Med. 2001)
... ... PUBLIC HEALTH: Lead is extremely toxic to the developing
nervous system, and high blood lead levels in children have been
a continuing problem in many cities in the US. Now a new report
indicates that the average blood lead levels in young children in
19 states decreased during the late 1990s. The proportion of
children tested who had blood lead levels equal to or greater
than 10 micrograms per deciliter declined from 10.5 percent to
7.6 per cent in 1998, although the proportion was higher in
certain counties. (CDCP Morb. Mort. Weekly Rep. 2001 50:337)
... ... MAMMALIAN EVOLUTION: "Synapsids" are the group of legged
vertebrates to which mammals belong. A new fossil skull of a
synapsid of extremely small size (estimated body mass
approximately 2 grams), unearthed in the Yunnan Province of China
and dated at approximately 195 million years old, has been
classified as representing a new lineage of mammaliaforms. The
skull length is 12 millimeters, and its anatomy extends the
earliest record of certain crucial mammalian features by
approximately 45 million years. (Science 2001 292:1535)
... ... BIOLOGY OF CANCER: Cancer development is believed to be
an evolutionary process involving replication, variation, and
selection within the body of an organism. Just as species are
shaped by the surrounding habitat, the properties of cancer cells
should mirror their somatic environment. A general explanation
for the elevated mutation rate that drives carcinogenesis has
been proposed, and a new experimental test of this hypothesis
demonstrates direct evolutionary relationships between
carcinogenic environments and specific types of genetic
instability. (Proc. Nat. Acad. Sci. 2001 98:5379,5770)
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2. ASTROPHYSICS: ON X-RAY POLARIMETRY OF ASTRONOMICAL OBJECTS
The conventional boundary between the shortest ultraviolet
radiation and x-rays is usually taken as the wavelength 10
nanometers. On the other end, the conventional boundary between
the shortest x-rays and the longest gamma rays is usually taken
as the wavelength 0.01 nanometers.
In general, x-ray spectral measurements show both the
composition and temperature of a source, and x-ray astrophysics
is an active area of research, with x-ray sources including both
stars and the centers of galaxies. The most intense astronomical
x-ray sources are extremely dense gravitational objects such as
neutron stars and black holes. Matter falling toward these
objects is heated to temperatures as high as 10^(10) kelvins,
resulting in x-ray and soft gamma-ray emissions. Because x-rays
are absorbed by the Earth's atmosphere, such measurements are
made above the atmosphere by apparatus carried by balloons,
rockets, or orbiting satellites.
Electromagnetic radiation involves the propagation of both
electric and magnetic forces, and at each point in a radiation
beam, there is a component electric field and a component
magnetic field, both of which oscillate in all directions
perpendicular to each other and to the direction in which the
beam is propagated. In plane-polarized radiation (linearly
polarized radiation), the component electric field oscillates as
in ordinary radiation except that the direction of oscillation is
contained within a plane. Likewise, in plane-polarized radiation,
the component magnetic field oscillates within a plane, the
planes in question being perpendicular. Circularly polarized
radiation has a component electric field that varies in direction
but not in magnitude, so that the field traverses a spiral path
in either a clockwise or counterclockwise direction. In general,
in astrophysics, polarization is a measure of the way in which
electromagnetic radiation from an astronomical object is affected
by factors such as scattering due to cosmic dust or strong
stellar or interstellar magnetic fields, or reflection from a
surface.
... ... E. Costa et al (6 authors at 2 installations, IT) report
the development of an improved sensitivity x-ray polarimeter for
the study of *black holes and *neutron stars, the authors making
the following points:
1) The authors point out that the study of astronomical
objects using electromagnetic radiation involves four basic
observational approaches: imaging, spectroscopy, photometry
(accurate counting of the photons received), and polarimetry
(measurement of the polarization of the observed photons. In
contrast to observations at other wavelengths, a lack of
sensitivity has prevented x-ray astronomy from making use of
polarimetry. Such a technique, however, could provide a direct
picture of the state of matter in extreme magnetic and
gravitational fields, and has the potential to resolve the
internal structures of compact sources that would otherwise
remain inaccessible. In *binary pulsars, for example, we could
directly "see" the rotation of the magnetic field and determine
the shape of the emission. Also, observation of the
characteristic twisting of the polarization angle in other
compact sources would reveal the presence of a black hole.
2) The authors report the development of an instrument that
makes x-ray polarimetry possible. The authors suggest that the
factor of 100 improvement in sensitivity they have achieved will
allow direct exploration of the most dramatic objects of the x-
ray sky.
... ... In a commentary on this work, Webster Cash (University of
Colorado Boulder, US) states: "X-ray astronomy has revealed some
of the most violent and compact spots in the Universe, such as
the surfaces of pulsars, the close orbits around giant black
holes, and the blast waves of *supernova explosions. By making
efficient use of the photons emitted by [dust and gas] disks
around black holes and other objects, x-ray astronomers have
successfully applied photometry, imaging, and spectroscopy to
these hot, energetic, and often variable sources. But polarimetry
is largely ignored at x-ray wavelengths because of the
inefficiency of existing instruments. The new x-ray polarimeter
developed by [Costa et al] promises to revolutionize space-based
observations."
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E. Costa et al: An efficient photoelectric x-ray polarimeter for
the study of black holes and neutron stars.
(Nature 7 Jun 01 411:662)
QY: E. Costa: costa@ias.rm.cnr.it
-----------
Webster Cash: A twisted look at the x-ray sky.
(Nature 7 Jun 01 411:644)
QY: Webster Cash: cash@casa.colorado.edu
-----------
Text Notes:
... ... *black holes: At the end of the life of a star, when the
nuclear fuel has been exhausted and the outward pressure can no
longer balance the inward-pulling gravitational forces, a series
of events occur, one of which is a "blowing-off" of considerable
stellar material. If the terminal stages of star death leave
a remnant star mass greater than approximately 3 solar masses,
the ultimate gravitational collapse will produce a black hole, a
relativistic singularity. A black hole is a localized region of
space from which neither matter nor radiation can escape. The
"trapping" occurs because the requisite escape velocity, which
can be calculated from the relevant equations, exceeds the
velocity of light and is therefore unattainable. Another view of
a black hole is that it is a mass that has collapsed to such a
small volume that its gravity prevents the escape of all
radiation.
... ... *neutron stars: If, following its terminal stages, the
remnant mass of a star is between 1.4 and approximately 3 solar
masses, the star will collapse into a neutron star, a body with a
radius of 10 to 15 kilometers, with a core so dense that its
component protons and electrons have merged into neutrons. The
average density of a neutron star is 10^(15) grams per cubic
centimeter, and the weight of an object on the surface of a
neutron star would be 10^(11) its weight on the surface of the
Earth. Neutron stars apparently have an outer shell of iron, but
it is iron like no Earth iron, an iron of 4 orders of magnitude
greater density.
... ... *binary pulsars: A pulsar is a pulsing source of stellar
radiation believed to originate with a neutron star. They were
originally discovered at radio wavelengths, but there are
optical, gamma-ray, and x-ray pulsars, and some of the gamma-ray
pulsars are extremely powerful gamma-ray emitters. A "binary
pulsar" is a pulsar in orbit with another star, the existence of
the companion revealed by a cyclic change in the pulse period as
the two stars orbit each other.
... ... *supernova: In general, a violent explosion in which
certain stars end their lives. The star may become more than
10^(9) times as bright as the Sun and may outshine its host
galaxy for weeks.
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Summary & Notes by SCIENCE-WEEK http://scienceweek.com 6Jul01
For more information: http://scienceweek.com/swfr.htm
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3. STATISTICAL PHYSICS: ON AGGREGATION
Atoms and molecules spontaneously aggregate into aerosols,
colloids, gels, clusters, and solids, the basis for the
aggregation a rearrangement of the entities of the system to
maximize interaction energies. Although the details of the
dynamics and endpoints of aggregating systems depend on the
nature of the atomic and molecular entities involved, models
based on simplifying assumptions have often proved to be of
considerable utility.
Marian von Smoluchowski (1872-1917), mentioned below, is
most famous for his theory of Brownian motion, developed
independently at approximately the same time as Einstein's more
famous theory, but Smoluchowski also made important contributions
to other areas of theoretical physics, particularly to theories
of diffusion and to theories of the physical properties of
colloidal systems.
... ... Andrew Zangwill (Georgia Institute of Technology, US)
presents a commentary on some recent theoretical work on
aggregating systems (J.G. Amar et al: J. Phys. Rev. Lett. 2001
86:3092), the author (Zangwill) making the following points.
1) The author (Zangwill) points out that in 1918, in a paper
published after his death, Smoluchowski proposed a theory of
aggregation that uses rate equations to describe the microscopic
processes of diffusion, collision, and irreversible coalescence
of multi-particle aggregates. The parameters of the equation, the
rate constants, determine how quickly the various kinetic
processes occur. Once these parameter are supplied, the theory
predicts how many large and small aggregates are present at any
moment in time, i.e., the time dependence of the cluster and size
distributions.
2) The author (Zangwill) points out that a convenient system
for comparing aggregation theory and experiment is the nucleation
and growth of vapor-deposited material on the surface of a single
crystal. In the earliest stages, before a single layer develops,
deposited atoms apparently diffuse on the bare surface and
aggregate into "islands" of one-atom thickness. The island-size
distribution as a function of the total amount of deposited
material can be measured by using a *scanning tunneling
microscope to image every island individually. Further, computer
simulations can be developed to track the motion of every
deposited atom as it makes a random walk across the surface to
finally attach irreversibly to an immobile island. Such computer
simulations, however, are difficult and computationally
expensive.
3) The author (Zangwill) points out that the achievement of
J.G. Amar et al (2001) is to demonstrate that the easier
Smoluchowski approach can also reproduce the experimental island-
size distributions, with the new theory capturing a significant
but subtle property of the measured size distributions, namely
dynamical scaling. In dynamical scaling, the size distributions
at different times collapse onto a single curve when plotted
using suitably scaled variables. The consequence is that the
normalized probability of finding an island on the surface with a
size equal to, for example, half of the average island size,
remains the same despite the fact that the average island size
changes with time.
4) Amar et al derive a set of rate equations for the
"capture zones" surrounding the islands, and then they combine
these equations with the usual Smoluchowski equations for the
island sizes by calculating the rate constants for the collision
processes, rather than introducing the collision-process rate
constants as parameters. The author (Zangwill) points out that an
intriguing aspect of the Amar et al rate-equation theory is that
it contains no randomness of any kind. "In this respect, their
work contrasts with recent computer simulations for the same
problem."
-----------
Andrew Zangwill: Advances in aggregation.
(Nature 7 Jun 01 411:651)
QY: Andrew Zangwill: andrew.zangwill@physics.gatech.edu
-----------
Text Notes:
... ... *scanning tunneling microscope: In scanning tunneling
microscopy, an atomically sharp metal tip is brought in atomic
proximity (e.g., 0.5 to 1 nanometer) to a flat surface so that
electrons can *tunnel between the two systems. The probe is
slowly moved across the surface and raised and lowered so as to
keep the tunneling current constant. A computer-generated contour
map of the surface is thus produced. The technique can resolve
individual atoms, but requires electrically conducting materials.
... ... *tunnel: "Tunneling" is a quantum mechanical phenomenon
involving an effective penetration of an energy barrier by a
particle resulting from the width of the barrier being less than
the wavelength of the particle.
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Summary & Notes by SCIENCE-WEEK http://scienceweek.com 6Jul01
For more information: http://scienceweek.com/swfr.htm
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4. BIOCHEMISTRY: ON THE STRUCTURE OF A PROTEIN BARREL
Although an argument can be made that the most important
chemical entities in biological systems are the proteins, at the
present time the relation between structure and function
(behavior) of proteins is for the most part a mystery. The usual
accompanying statement is that proteins are "complex". But
consider the following: Although an ordinary office building has
millions of interconnected parts, any skilled architectural
engineer can look at one of those parts in the context of the
building and make a reasonable statement concerning the relation
of that part to some global function of the building -- to the
structure keeping it upright, to the heating, electricity, light,
space, and so on. In contrast, an ordinary protein may consist
of, for example, 30,000 atoms or less -- a number of fundamental
components considerably smaller than the number of such
components in an office building, and with no greater degree of
connectivity. Nevertheless, no biochemist can make statements
about the constituent parts of a protein equivalent to the
statements that an architectural engineer can make about the
constituent parts of an office building.
The problem is really not "complexity" but the degree of
knowledge: the office building is constructed according to a
human plan, with individual parts selected to complete the plan,
the building constructed by _forward_ engineering, and this
process and the functions of the various interconnecting parts in
the building are in general known to any trained architectural
engineer. With a protein, however, the biochemist is provided
with a structure from the start and asked to take the structure
apart and understand how the structure and its components relate
to the function of that protein. That is _reverse_ engineering, a
process usually of much greater difficulty than forward
engineering, and in this case it is reverse engineering without
much knowledge of fundamental principles comparable to the
fundamental principles of architectural engineering. The so-
called "complexity" of proteins is thus apparently based on our
lack of knowledge of the principles that relate component parts
to global function.
All of the above is merely a preamble to the following: a)
As important as proteins are in biological systems, we know
relatively little about them. b) Protein chemistry is an
advancing field involving intensive research on many fronts
ranging from theoretical chemistry to experimental manipulations
in biological systems. c) Given our present inadequate knowledge,
each piece of solid information about the relation between
structure and function in proteins is a nugget, an item of
information to be analyzed and conserved for future possible use
in the formulation of fundamental principles.
In this context, the term "alpha helix" refers to a spiral
configuration of a polypeptide chain in which successive turns of
the helix are held together by hydrogen bonds between the amide
(peptide) links, the carbonyl group of any given residue being
hydrogen-bonded to the imino group of the 3rd residue behind it
in the chain. The term "beta sheet" (beta-pleated sheet) refers
to an array of two or more "beta strands", with each beta strand
consisting of two polypeptide chains in a so-called "beta
configuration", which in turn is a stable configuration of a
polypeptide chain in which the chain is almost fully extended and
hydrogen-bonded to an adjacent polypeptide chain.
In general, the structures of biopolymers are denoted as
follows: 1) Primary structure: The sequence of subunits that
comprise the macromolecule (e.g., the amino acid sequence of a
protein). 2) Secondary structure: The localized arrangement in
space of regions of a biopolymer (e.g., the alpha-helix). 3)
Tertiary structure: The 3-dimensional configuration of a
biopolymer. 4) Quaternary structure: The 3-dimensional
arrangement and constitution of a multimeric macromolecule (i.e.,
a substance containing more than one biopolymer; an entity
consisting of biopolymer subunits.
... ... J.A. Silverman et al (3 authors at Stanford University,
US) present an experimental analysis of a particular protein
domain conformation, the authors making the following points:
1) The authors point out that the "[beta/alpha](sub8)
barrel" (BA8-barrel) is the most common fold among protein
catalysts, appearing in approximately 10 percent of all known
enzyme structures. This barrel structure is composed of 8
catenated strand-loop-helix-turn units. The beta-strands are
located in the interior of the protein, forming the staves of a
barrel, whereas the alpha-helices pack around the exterior. The
active sites of all known BA8-barrel enzymes are located in the
beta-alpha loops.
2) The authors point out that the "oil-droplet" and "jigsaw-
puzzle" models of protein folding offer two limiting views of how
an amino acid sequence could encode a globular structure. An oil-
droplet model proposes that partitioning of hydrophobic and polar
amino acids into oil and water phases during protein folding
forces appropriate secondary and tertiary structure to form. In
the extreme view, the pattern of hydrophobic and polar residues
in an amino acid sequence (the "H/P pattern") is sufficient to
specify a 3-dimensional conformation. In contrast, a jigsaw-
puzzle model proposes that amino acids in a protein structure fit
together with perfect shape (and chemical) complementarity.
Specific interactions between residues distant in sequence are
presumed to pin the structure together, these interactions
depending on the stereochemical details of amino acid chains,
such as shape and charge, rather than on simple hydrophobic or
polar character.
3) To investigate which sequence elements specify the BA8
fold, the authors examined by gene mutation in yeast every
structural residue in the canonical BA8-barrel protein
triosephosphate isomerase (TIM). The study investigated a total
of 182 amino-acid sites in the enzyme for their tolerance or
intolerance to substitution. The authors report that at 97 of the
182 structural positions analyzed, mutational change of the
normal ("wild-type") amino acid to a particular one of 7 amino
acids had no measurable effect on the activity of the enzyme. The
7-amino acid repertoire that could provide an amino acid that
could take the place of the wild-type amino acid were
phenylalanine, valine, leucine, alanine, lysine, glutamic acid,
glutamine. At an additional 45 positions, the wild-type amino
acid was already one of the 7 residues. Thus, 142 of the 182
structural positions could be readily reduced to a 7-letter
amino-acid alphabet. Fifteen of the remaining positions are
phylogenetically variable, although these experiments did not
directly measure the effects of substitution at these positions.
The authors suggest that given these results, it seems likely
that triosephosphate isomerase, and perhaps BA-8 barrels
generally, could be encoded with a simplified amino-acid
alphabet.
... ... In a commentary on this work, Neville Kallenbach (New
York University, US) states: "Technically, the report by
Silverman et al (2001) is a tour de force... This is a landmark
study, showing that large protein structures are now amenable to
rigorous testing of hypotheses about folding... The achievement
of [the authors] is that they open the way to answering
fundamental questions about how large and complex enzymes fold,
function, achieve their stability -- even evolve -- and how they
might be engineered for biochemical or chemical applications."
-----------
J.A. Silverman et al: Reverse engineering the [beta/alpha](sub8)
barrel fold.
(Proc. Natl. Acad. Sci. US 13 Mar 01 98:3092)
QY: P.B. Harbury: harbury@cmgm.stanford.edu
-----------
Neville Kallenbach: Breaking open a protein barrel.
(Proc. Natl. Acad. Sci. US 13 Mar 01 98:2958)
QY: Neville Kallenbach: neville.kallenbach@nyu.edu
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 6Jul01
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
ON EXPLANATIONS OF PROTEIN FOLDING
Since the 3-dimensional configuration of a protein is an
essential determinant of what the protein does in a biological
system, protein "folding", the process that leads to this
configuration, is a central focus in biophysical chemistry.
... ... William A. Eaton (National Institutes of Health, US)
presents a review of current research in this field, the author
making the following points:
1) There are two aspects to the problem of protein folding.
The first is predicting the 3-dimensional structure of a protein
from its amino acid sequence; the second is to understand _how_
proteins fold. The problem of protein folding has recently
assumed additional importance as more and more human diseases
(e.g., Alzheimer's and Parkinson's diseases) are believed to be
caused by aggregation of misfolded proteins.
2) The question of _how_ a protein folds can be phrased more
precisely as follows: What are the sequences of structural
changes that occur in a polypeptide as it finds its way from the
myriad of possible structures in the *denatured state to the
final unique *native structure? How many different folding routes
exist, and what are their relative probabilities?
3) Until approximately a decade ago, the problem of
understanding how proteins fold was addressed by identifying and
characterizing one or two metastable structures believed to be
obligatory intermediates in a sequential process along a well-
defined protein-folding pathway. The prevailing view was that
structural characterization of such intermediates would give the
clue to the basic underlying mechanism, as in the study of
organic chemical reactions. However, unlike small-molecule
chemical reactions, in which covalent bonds are broken and new
bonds formed in a structurally well-defined transition state, the
many degrees of freedom of a polypeptide chain demand a different
approach. A polypeptide of 100 amino acids has a huge number of
conformations, even if only a tiny fraction of the more than
2^(100) (= 10^(30)) possible conformations are thermally
occupied. Understanding the complexities of protein folding at
the microscopic level, and developing models that make
quantitative predictions, therefore requires a statistical
approach, i.e., the theoretical and computational tools of modern
statistical mechanics.
4) Nonexponential kinetics have played an important role in
understanding conformational changes in native proteins. They are
particularly interesting for protein folding because they could
arise from a process that is "downhill" in free energy, i.e, one
in which the overall free energy barrier separating the native
from the denatured state is very small or nonexistent. For large
barriers, only the structures of the initial and final states are
observable, because structures along the folding route are too
sparsely populated. If, however, the barrier becomes very small
or disappears altogether, all of the structures can in principle
be detected and characterized by spectroscopy.
5) At the present time, there exists the exciting prospect
of performing single molecule experiments for direct exploration
of the energy landscape and folding routes. Finding proteins that
fold with a "downhill scenario" is an essential first step in
this quest. That some proteins will exhibit downhill folding,
moreover, is one of the novel theoretical predictions of an
energy landscape analysis of protein folding.
-----------
Editor's note: In addition to the background material below, see
the 8 Aug 99 issue of SW (#32), report #3)
-----------
William A. Eaton: Searching for "downhill scenarios" in protein
folding.
(Proc. Natl. Acad. Sci. US 25 May 99 96:5897)
QY: William A. Eaton [eaton@helix.nih.gov]
-----------
Text Notes:
... ... *denatured state: In biochemistry, the term
"denaturation" refers to the complete unfolding
and loss of catalytic activity of a protein.
... ... *native structure: The "native" structure or
configuration of a biological macromolecule is the functional
state or configuration ordinarily assumed by the molecule in the
biological system in which the molecule occurs.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 3Sep99
-------------------
Related Background:
ON THE CHEMICAL PHYSICS OF PROTEIN FOLDING
... ... C.L. Brooks et al present a short review of protein
folding from the perspective of chemical physics, and with a
focus on the work of their own group, the authors make the
following points: 1) The question of the mechanism of protein
folding was once thought to be entirely analogous to the question
of mechanism in intermediary metabolism or classical organic
chemistry: the essential classical idea was that a protein
folding pathway involves a series of discrete intermediates. Such
discrete intermediates do occur in the late stages of protein
folding, but to answer the practical questions of structure
prediction and design, a new viewpoint on folding is required. 2)
The authors suggest this new viewpoint is that of chemical
physics rather than that of classical chemistry, and that the
chemical physics view requires a new set of theoretical ideas,
computational techniques, and major advances in experimental
methodology. 3) The authors suggest the theoretical framework for
the new chemical physics approach to protein folding should be
that of "*energy landscape theory", which asserts that "a full
understanding of the folding process requires a global overview
of the energy landscape." 4) The authors propose that the protein
folding energy landscape resembles a partially rough funnel
riddled with energy traps where the protein can transiently
reside. There is no unique pathway but a multiplicity of
convergent folding routes toward the native state... The authors
state that the essence of the funnel energy landscape idea is
competition between the tendency toward the folded state and
trapping because of "ruggedness" of the funnel. 5) Concerning
theoretical modeling, the authors point out that simulations with
detailed atomic models are extremely intensive numerically, so
that the number and size of systems that can be studied is
limited. Simulation models of intermediate complexity have
therefore been used. 6) Concerning experimental approaches to
exploring the energy landscape of protein folding, there are
various new methods involving the physical monitoring of folding
from an unfolded state, for example, monitoring in the
microsecond range following initiation of folding by a
nanosecond-scale step-change in ambient temperature. The authors
conclude: "Experiments are beginning to build up a *phase diagram
of folding kinetics that can be used to test and refine
theoretical models."
-----------
C.L. Brooks et al (4 authors at 3 installations, US)
Chemical physics of protein folding.
(Proc. Natl. Acad. Sci. US 15 Sep 98 95:11037)
QY: Charles L. Brooks, Scripps Research Institute 619-784-1000.
-----------
Text Notes:
... ... *energy landscape: The "energy landscape" here refers to
the contours of what is essentially a classical energy/entropy
diagram, with the native configuration state positioned at the
bottom of a deep potential well, in this case a funnel with sides
containing miniature energy wells or "traps".
... ... *phase diagram: A classical graphical representation of
the equilibrium relationships between phases of a chemical
system.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 23Oct98
For more information: http://scienceweek.com/swfr.htm
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
5. MEDICAL BIOLOGY:
MIDLIFE REDUCED ACTIVITY IN ALZHEIMER'S DISEASE
Alzheimer's disease is now tabulated as the 12th leading cause of
death in the US, with a 1997 death-rate per 100,000 population of
8.4, which is higher than homicide and legal intervention (7.0),
AIDS (6.2), and atherosclerosis (6.2). It is estimated that by
2025 more than 20 million people worldwide will be afflicted with
the disease. In general, Alzheimer's disease is a degenerative
brain disorder that develops in mid- to late-adult life, the
disease resulting in a progressive and irreversible decline in
memory coupled with a decline in various other cognitive
functions. In terms of general pathology, the disease is
characterized by the destruction of nerve cells and neural
connections in the cerebral cortex of the brain and by a visible
and significant loss of brain mass.
... ... R.P. Friedland et al (8 authors at 2 installations, US)
present a study of activity of Alzheimer's disease patients in
midlife compared with a healthy control-group, the authors making
the following points:
1) The authors point out that research in North America,
Europe, Asia, and the Middle East has demonstrated that the
*incidence and prevalence of Alzheimer's disease is lower in
subjects with relatively higher levels of education. According to
one study (the East Boston study), each year of education reduces
the risk of Alzheimer's disease by 17 percent. Although the
protection against the development of Alzheimer's disease
provided by education could be an artifact produced by the
ability of more highly educated persons to perform better on
cognitive tests, many studies have used functional rather than
psychometric measures for diagnosis and have documented the
protective effect of education. Although the mechanisms of
education protection remain unknown, it has been proposed that
the protective effects of education are related to neuronal
reserve, with individuals with higher levels of education more
resistant to the effects of the disease on cognition because of
enhanced synaptic complexity. Occupational attainment also has
been demonstrated to be protective against the disease.
2) The authors point out that education protection also may
be induced by lifelong patterns of neuronal activation associated
with exposure to education. But education and occupation are not
the only reflection of these lifelong patterns: recreational
activities are also indications of the ways in which cognitive
and other skills are used in daily life. The authors have
hypothesized that recreational tasks, in addition to education
and occupation, are protective against the development of
Alzheimer's disease. Leisure endeavors are reflective of the
intrinsic value of an activity for an individual -- they may be
more reflective of neurological factors than education or
occupation, which are strongly influenced by socioeconomic
determinants, especially in the earlier years of this century,
when economic, social, and military factors often determined who
went to school and for how long. Recreational activities thus may
provide a reflection of neuronal reserve and activation that may
be relatively independent of these economic, social, and military
factors.
3) The authors report their results indicate that patients
with Alzheimer's disease are less active in midlife (early and
middle adulthood) in terms of intellectual, passive, and physical
activities than members of the control group used in this study.
The lower activity levels prior to onset of disease (premorbid
levels) in patients with Alzheimer's disease persisted in
measures of intellectual, passive, and physical activities,
calculated by using an independently developed scale following
statistical correction for year of birth, sex, education, and
income adequacy. These differences were not explained by
differing educational levels in the two groups. The study
minimized the influence of early disease on participation in
activities by the collection of data only concerning the period
of midlife ending at age 60 or ending 5 years before disease
onset (whichever was earlier). The authors suggest their results
indicate that low participation in activities in midlife (in
addition to low levels of educational and occupational
achievement) is a risk factor for the disease.
-----------
R.P. Friedland et al: Patients with Alzheimer's disease have
reduced activities in midlife compared with healthy control-group
members.
(Proc. Natl. Acad. Sci. US 13 Mar 01 98:3440)
QY: R.P. Friedland: rpf2@po.cwru.edu
-----------
Text Notes:
... ... *incidence and prevalence: In this context, the term
"incidence" refers to the number of new cases during a specified
time period; the term "prevalence" refers to the total number of
existing cases at a specified time or during a specified time
period.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 6Jul01
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
MEDICAL BIOLOGY: ALZHEIMER'S DISEASE
... ... Peter H. St. George-Hyslop (University of Toronto, CA)
presents a review of current research on the biology of
Alzheimer's disease, the author making the following points:
1) The author points out that post-mortem histological
analysis of the brains of patients with Alzheimer's disease
reveals loss of nerve cells in specific regions of the brain,
such as the hippocampus, a center for memory, and the cerebral
cortex in general, the brain structure most involved in
reasoning, memory, language, and other important cognitive
processes.
2) The second directly observable hallmark of Alzheimer's
disease is the prevalence of clusters of specific proteins in the
brain. These accumulations occur in two forms: those found inside
nerve cells (so-called "neurofibrillary tangles") and those found
outside nerve cells (so-called "amyloid plaques").
3) Investigation of amyloid plaques has revealed that a
principal component is a peptide ("beta-amyloid peptide) of 40 to
42 amino acids, this peptide derived from a longer protein (beta-
amyloid precursor protein [betaAPP]) whose gene has been
sequenced. The isolation of the beta-amyloid peptide and the
isolation of the gene for beta-amyloid precursor protein were
quickly followed by the discovery that the precursor protein gene
is located on chromosome 21, the same chromosome involved in Down
syndrome, another neurodegenerative disorder.
4) Although the precise biological role of normal beta-
amyloid precursor protein remains obscure, it is known that many
kinds of cells and tissues produce this protein, and that the
protein ranges from 695 to 770 amino acids in length. The protein
apparently spans the cell membrane, with a short segment jutting
into the cell interior and a longer segment jutting into the
extracellular space. The beta-amyloid peptide is apparently
snipped out of the section of the precursor protein that spans
the cell membrane. Research has revealed there are two possible
snipping processes: a) the precursor protein is first cleaved by
an apparent enzyme (alpha-secretase), then cut by another
apparent enzyme (gamma-secretase), and together these cuts
produce a harmless peptide fragment called "p3"; b) in a second
possible process, an enzyme that has now been isolated (beta-
secretase) clips the precursor protein, one of the resulting
pieces is then snipped by gamma-secretase, and the result is the
beta-amyloid peptide. Under ordinary conditions, most beta-
amyloid strings contain 40 amino acids. But a small number (less
than 10 percent) have two extra amino acids, and it has been
demonstrated that this slightly longer form is the form that
gives rise to plaques and the form that has a direct toxic effect
on neurons.
5) The idea of changes in beta-amyloid precursor protein as
central to Alzheimer's disease gained further support with the
discovery of mutations in a set of genes that interfere with the
cutting of the precursor protein. Disruptions in the genes
presenilin-1 and presenilin-2, genes that are located on
chromosome 14 and chromosome 1, respectively, cause a very
aggressive form of early-onset Alzheimer's disease. (Early-onset
forms are generally seen in approximately 10 to 60 percent of
patients with familial Alzheimer's disease.) Both genes encode
proteins that span the cell membrane several times, and these
proteins apparently undergo a complicated maturation process,
during which they are cut into two pieces that are in turn
incorporated into a protein complex involved in cutting other
membrane-bound proteins, such as beta-amyloid precursor protein.
6) The author concludes: "The biochemical, molecular,
genetic, epidemiological, and clinical discoveries of the past 10
years or so have significantly advanced our understanding of the
mechanisms underlying Alzheimer's disease and make it
increasingly likely that, in the years to come, useful treatments
will be generated."
-----------
Peter H. St. George-Hyslop: Piecing together Alzheimer's.
(Scientific American December 2000)
QY: Peter H. St. George-Hyslop: University of Toronto, CA.
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 12Jan01
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
ALZHEIMER'S DISEASE: INTERHEMISPHERIC DISCONNECTION SYNDROME
The term "dementia" refers to a structurally caused permanent or
progressive decline in several dimensions of intellectual
function, the decline interfering substantially with the
individual's normal social or economic activity. There are
various forms of dementia produced by various causes. Alzheimer-
type dementia (Alzheimer's disease) is due to what appear to be
specific cellular and histological degenerative processes, with
loss of cells from the *basal forebrain, cerebral cortex, and
other brain areas, and the brain showing moderate to marked
atrophy. Memory loss is the most prominent early symptom.
... ... Lakmache et al (5 authors at 3 installations, CA) now
report evidence indicating that patients diagnosed as possessing
Alzheimer's disease show deficits in interhemispheric integration
of information, probably reflecting a *corpus callosum
dysfunction. The study involved 10 Alzheimer's disease patients
and 10 matched controls. Patients were given a battery of motor,
somatosensory, and visual tests that required use of either one
or both cerebral hemispheres. Tasks were chosen such that
subjects with Alzheimer's disease performed normally when using
intrahemispheric processing. The same subjects, however,
performed poorly when interhemispheric communication was
required. The authors suggest their observations indicate the
presence of a "disconnection syndrome", and that these
interhemispheric tasks can serve as diagnostic tools for the
early assessment of Alzheimer-type dementia.
QY: Yamina Lakmache, University of Montreal (Psychologie),
C.P.6128, Succursale Centre-Ville, Montreal PQ, H3C 3J7 CA.
(Proc. Natl. Acad. Sci. US 21 Jul 98 95:9042)
(Science-Week 28 Aug 98)
-------------------
Related Background:
... ... *basal forebrain: The forebrain (prosencephalon,
proencephalon) is the largest major division of the human brain,
and apparently associated with the highest intellectual
functions.
... ... *corpus callosum: The large band of nerve fibers that
serves as the primary connection between the two halves of the
brain.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 28Aug98
For more information: http://scienceweek.com/swfr.htm
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6. MEDICAL BIOLOGY: TULAREMIA AS A BIOLOGICAL WEAPON
Although political events during the past decades have
reduced fears of biological warfare among the major powers, the
pathogens likely to be used in such warfare have not vanished,
and there is now an apparent growing concern about the use of
such pathogens in acts of biological terrorism ("bioterrorism").
The bacterial pathogen Francisella tularensis is widely
found in various animals and is ordinarily transmitted to humans
by biting arthropods, direct contact with infected animal tissue,
inhalation of aerosols, or ingestion of contaminated food or
water. The resulting disease, tularemia, is usually characterized
by profound systemic symptoms, and the illness may lead to death
if untreated.
... ... D.T. Dennis et al (18 authors at 8 installations, US)
present a review of tularemia as a biological weapon, the authors
making the following points:
1) The authors point out that the causative agent of
tularemia, F. tularensis, is one of the most infectious
pathogenic bacteria known, requiring inoculation or inhalation of
as few as 10 organisms to cause disease. Humans become
incidentally infected through diverse environmental exposures and
can develop severe and sometimes fatal illness, but they do not
transmit infection to others.
2) Tularemia was first described as a plague-like disease of
rodents in 1911, and soon after it was recognized as a
potentially severe and fatal illness in humans. The epidemic
potential of tularemia became apparent in the 1930s and 1940s,
when large waterborne outbreaks occurred in Europe and the Soviet
Union and cases associated with animal outbreaks occurred in the
US. In addition, F. tularensis quickly gained notoriety as a
virulent laboratory hazard, and the pathogen has long been
considered a potential biological weapon.
3) F. tularensis was one of the agents studied at Japanese
germ warfare research units operating in Manchuria between 1932
and 1945, and it was also examined for military purposes in the
West. It has been suggested that tularemia outbreaks affecting
tens of thousands of Soviet and German soldiers on the eastern
European front during World War II may have been the result of
intentional use.
4) Following the World War II, there were continuous
military studies of tularemia, and in the 1950s and 1960s, the US
military developed weapons that would disseminate F. tularensis
aerosols. By the late 1960s, F. tularensis was one of several
biological weapons stockpiled by the US military.
5) In 1969, an expert committee of the World Health
Organization estimated that an aerosol dispersal of 50 kilograms
of virulent F. tularensis over a metropolitan area with 5 million
inhabitants would result in 250,000 incapacitating casualties,
including 19,000 deaths. Illness would be expected to persist for
several weeks and disease relapses to occur during the following
weeks or months.
6) The US terminated its biological weapons development
program by executive order in 1970, and by 1973 the entire US
biological arsenal had been destroyed.
7) The Soviet Union apparently continued stockpiling F.
tularensis as a biological weapon into the early 1990s, with
weapons production of F. tularensis strains engineered to be
resistant to antibiotics and vaccines.
8) The US Centers for Disease Control and Prevention
recently examined the expected economic impact of bioterrorism
attacks and estimated the total base costs to society of an F.
tularensis aerosol attack to be $5.4 billion for every 100,000
persons exposed.
9) The authors conclude: "A weapon using airborne tularemia
would likely result 3 to 5 days later in an outbreak of acute,
undifferentiated febrile illness with incipient pneumonia,
*pleuritis, and *hilar lymphadenopathy... Without treatment, the
clinical course could progress to respiratory failure, shock, and
death."
-----------
D.T. Dennis et al: Tularemia as a biological weapon.
(J. Amer. Med. Assoc. 6 Jun 01 285:2763)
QY: David T. Dennis: dtd1@cdc.gov
... ... *pleuritis: (pleurisy) Inflammation of the pleura, the
membranes enveloping the lungs and lining the wall of the chest
cavity.
... ... *hilar lymphadenopathy: In general, a "hilum" is a
part of an organ where nerves and blood vessels enter and leave.
The term "lymphadenopathy" refers to any disease process
affecting lymph nodes.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 6Jul01
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
ON BIOLOGICAL TERRORISM
... ... Donald A. Henderson (Johns Hopkins University, US)
presents a review of current views, expectations, and contingency
plans concerning biological terrorism, the author making the
following points concerning the scientific fundamentals:
1) The expected scenario following release of an aerosol
cloud of a biological agent is entirely different from that
following an attack of nuclear or chemical terrorism. A
biological agent aerosol release could be silent and would almost
certainly be undetected. The cloud would be invisible, odorless,
and tasteless. It would behave much like a gas in penetrating
interior areas, and the release would not be suspected for days
or weeks later.
2) The implicit assumption has frequently been that chemical
and biological threats and the responses to them are so
generically similar that they can be readily handled by a single
"chembio" expert, usually a chemist. This is a serious
misapprehension.
3) Any of thousands of biological agents that are capable of
causing human infection could be considered a potential
biological weapon, but realistically only a few pose serious
problems. Only a very small number of species of these pathogens
can be cultivated and dispersed effectively so as to cause cases
and deaths in numbers that would threaten the functioning of a
large community. The current consensus is that there are 11
pathogens "very likely to be used." *Smallpox, *plague, *anthrax,
and *botulism are considered the top four candidates. The others
are *tularemia, *glanders, *typhus, *Q fever, *Venezuelan equine
encephalitis, *Marburg virus, and *influenza virus.
4) Any group with sufficient resources could purchase
prepared supplies of aerosolizable organisms and could transport
them easily, because only small quantities are needed to inflict
casualties over a wide area. No mechanisms currently exist for
screening to intercept such materials at state or national
borders.
5) Of the potential biological weapons, smallpox and anthrax
pose by far the greatest threats, but these pathogens have
different clinical and epidemiological properties. Smallpox poses
an unusually serious threat, in part because virtually everyone
is now susceptible, vaccination having stopped worldwide 20 or
more years ago as a result of the eradication of the disease. It
is probable that no more than 20 percent of the world population
is protected; for the unprotected, fatality rates after infection
are 30 percent. Another problem is that there are no longer any
manufacturers of smallpox vaccine, which means large-scale
vaccination immediately after an outbreak is currently not
possible.
6) Concerning an inhalation anthrax epidemic, the scenario
is as dangerous as that for smallpox. After 2 to 3 days
anthrax-infected individuals would appear in emergency rooms and
doctors' offices with a variety of nonspecific symptoms such as
fever, cough, and headache. Within a day or two, patients would
become critically ill and then die within 24 to 72 hours. The
fatality rate for anthrax is 80 percent or greater.
7) The author concludes: "Once the medical community
rallied... in educating peoples and policymakers everywhere about
the dread realities of a nuclear winter. Perhaps the same should
now be done with respect to the realities of biological weapons,
which are now considered to be a more serious threat than the
nuclear ones."
-----------
Donald A. Henderson: The looming threat of bioterrorism.
(Science 26 Feb 99 283:1279)
QY: Donald A. Henderson, Johns Hopkins Center for Civilian
Biodefense Studies, Johns Hopkins Univ., Baltimore, MD 21202 US.
-----------
Text Notes:
... ... *Smallpox: This is an acute eruptive contagious disease
caused by a poxvirus (Orthopoxvirus, a member of the family
Poxviridae). The average incubation period is 8 to 14 days.
Following the incubation period, the onset symptoms are
constitutional: chills, high fever, backache, headache. In from 2
to 5 days, these symptoms subside and the skin eruptions appear.
Considering the temporal course of the disease, a smallpox
epidemic would probably not become evident until 2 to 3 weeks
after release of an aerosol.
... ... *plague: In this context, this term refers to the acute
infectious disease caused by the bacterium Yersinia pestis, the
disease marked by high fever, toxemia, and prostration. The
pathogen is usually transmitted to man by fleas that have bitten
infected rodents, and there are various forms of the disease. The
incubation period is 2 to 7 days. The fatality rate is near 50
percent, with usually 100 percent fatality for the pneumonic form
of the disease.
... ... *anthrax: This disease is caused by the bacterium
Bacillus anthracis, and is usually transmitted by infected
animals through traumatized human skin. The disease is marked by
hemorrhage and blood effusions in various organs and body
cavities, and by symptoms of extreme prostration. In the context
of this report, the disease entity of concern is "inhalation
anthrax", which is a more serious human disease than anthrax
contracted from an animal through the skin. Inhalation anthrax
produces hemorrhagic pneumonia with shock and is usually fatal
(fatality above 80 percent).
... ... *botulism: This disease is caused by toxins of the
bacterium Clostridium botulinum, an organism common in soil and
sometimes in animal feces. Symptoms appear 18 to 24 hours after
entry of the toxins, and the most severe symptoms are the result
of effects on the neuromuscular system. Death occurs from
respiratory paralysis or cardiac arrest. The fatality rate is
high. Ordinarily, botulism is not an actual human infection,
since the human disease is almost always caused by ingestion of
food contaminated with toxins produced by C. botulinum, which is
anaerobic and grows only under conditions of low or absent oxygen
(e.g., in canned foods). The botulinum toxins are among the most
highly toxic substances known: the lethal dose for a human is
estimated to be in the range 1 to 2 micrograms.
... ... *tularemia: This disease is caused by the bacterium
Francisella tularensis, a pathogen usually transmitted to humans
by biting arthropods (e.g., insects), direct contact with
infected animal tissue, ingestion of contaminated food or water,
and inhalation of aerosols. Apparently, inhalation of only 50
individual F. tularensis bacteria can result in infection.
Symptoms appear within a week. The disease can usually be
controlled with antibiotics.
... ... *glanders: A common disease of horses, mules, and
donkeys, caused by the bacterium Burkholderia mallei. The
inhalation form of the disease may lead to primary pneumonia.
The disease can usually be controlled with antibiotics.
... ... *typhus: A group of acute infectious and contagious
diseases caused by the bacterial group Rickettsaie. These
diseases are characterized by fever, headache, malaise, and
prostration.
... ... *Q fever: Also caused by a Rickettsaie bacterium, but the
symptoms resemble influenza, nonbacterial pneumonia, hepatitis,
or encephalopathy.
... ... *Venezuelan equine encephalitis: This is a viral disease
usually transmitted by mosquitoes from horses to humans. It is
caused by a togavirus, subgroup alphavirus. In humans, the
symptoms are similar to those of influenza.
... ... *Marburg virus: One of the two notorious African
Hemorrhagic Fevers (the other is Ebola virus), highly virulent,
with infections usually ending in death. These viruses have the
highest mortality rate (as much as 90 percent) of all the viral
hemorrhagic fevers. The disease was first recognized in 1967.
... ... *influenza virus: Any of a group of influenza viruses,
all of the family Orthomyxoviridae. The influenza diseases
usually have a sudden onset, are highly contagious, and easily
produce large-scale epidemics. Apparently, if only a few cells of
the respiratory *epithelium are infected by deposited virus
particles, the infection can proceed. The severity of symptoms
and the outcome depends on which strain of the virus is the
pathogen.
... ... *epithelium: In animals and humans, epithelial cells
compose the cell layers that form the interface between a tissue
and the external environment, for example, the cells of the skin,
the lining of the intestinal tract, and the lung airway passages.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 21May99
For more information: http://scienceweek.com/swfr.htm
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7. IN FOCUS: ON CHIMPANZEES
"Evolutionary scientists are therapists for the human species.
People go to therapy to explore what molded them into who they
are today. That desire, writ large, is exactly what the study of
human origins is all about. A word of warning... Both lay
[people] and scientists misread evolution's signature easily and
often. Chimpanzees are not evolutionary challenged people, and
people did not evolve from gorillas. They and we share a common
ancestor in the nearly invisible past, a past that we try to
reconstruct in hopes of catching a sidelong glimpse of that
chimerical great grandparent. There are amazing similarities
between us today, but also profound differences. While they may
look like hirsute, sloped-foreheaded, primitive humans,
chimpanzees evolved for some 5 million years after their
ancestors diverged from our own. I offer a cautionary shout to
all those seeking to extrapolate from apes to humans and vice
versa: the great apes are highly evolved in their own right. They
inform us of the range of paths taken by our ancestors long ago.
This gives us an extraordinarily richer view of humanity than we
could have otherwise, but it can also deceive us if we are not
careful. At every turn, [we] should remember that humans,
chimpanzees, gorillas, bonobos, orangutans and all other higher
primates evolved for equally unique reasons. If we are going to
understand the meaning of the term "human nature", we must get to
the heart of what apes can and cannot tell us about our own
cognitive abilities and behavioral tendencies. No claim in
science is at once more banal and more profound than that of
human uniqueness. Explaining human uniqueness is what
anthropologists do for a living. At the same time, primatologists
are fond of asserting that apes are more like people than people
like to admit. Somewhere between these two claims is evidence of
the shared and separate ancestry of humans and their genetic
kin."
-----------
Craig Stanford: _Significant Others: The Ape-Human Continuum and
the Quest for Human Nature_
(Basic Books, New York 2001, p.xv)
[The author is Associate Professor of Anthropology at the
University of Southern California and Director of the Bwindi-
Impenetrable Great Ape Project, Uganda.]
http://www.amazon.com/exec/obidos/ASIN/0465081711/scienceweek
-------------------
SCIENCE-WEEK http://scienceweek.com 6Jul01
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8. FROM THE SCIENCEWEEK ARCHIVE:
ON GENES AND BEHAVIOR
---------------------
ANIMAL BEHAVIOR: NONGENOMIC TRANSMISSION OF MATERNAL BEHAVIOR
The question of genetic vs. non-genetic determinants of behavior
is an area of controversy in several branches of science, and as
can be seen from the background material attached to this report,
discussion of the question is on occasion contentious. In humans,
individual differences in personality traits often appear to be
transmitted from parents to offspring, and a critical question
concerns the mode of transmission of such traits. Studies of
identical (monozygotic) and non-identical (dizygotic) twins have
provided some evidence for a genetic mechanism of transmission of
even complex personality traits. In contrast to genomic
transmission, parental behavior influences the development of
offspring and could therefore serve as a mechanism for a non-
genomic behavioral mode of transmission of traits. In rats, for
example, it has been known for nearly 50 years that variations in
maternal care are associated with the development of individual
differences in behavioral and endocrine responses to stress in
the offspring, and this species has served as an animal model in
many studies of the effects of variations in maternal care on the
behavior of offspring.
... ... D. Francis et al (4 authors at McGill University, CA)
now present cross-fostering studies examining the possibility
that variations in rat maternal care might be the mechanism for a
behavioral transmission of individual differences across multiple
generations. In the experimental and control protocols, no more
than 2 of 12 rat pups were fostered into or from any one litter.
The authors report their results provide evidence for 1) a causal
relationship between maternal behavior and stress reactivity in
the offspring; and 2) the transmission of such individual
differences in maternal behavior from one generation of females
to the next. In addition, the authors report that an
environmental manipulation imposed during early development that
alters maternal behavior can affect the pattern of transmission
in subsequent generations. The authors suggest that taken
together, these results indicate that variations in maternal care
can serve as the basis for a non-genomic behavioral transmission
of individual differences in stress reactivity across
generations. The authors conclude: "In humans, social, emotional,
and economic contexts influence the quality of the relationship
between parent and child and can show continuity across
generations. Our findings in rats may thus be relevant in
understanding the importance of early intervention programs in
humans."
-----------
D. Francis et al: Nongenomic transmission across generations of
maternal behavior and stress responses in the rat.
(Science 5 Nov 99 286:1155)
QY: Michael J. Meaney: mdmm@musica.mcgill.ca
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 25Feb00
-------------------
Related Background:
GENETIC CONTROL OF SOCIAL ORGANIZATION IN ANTS
Biological evolution is marked by a number of major transitions,
one of which is the evolution of complex social behavior. Animal
social life can take a variety of forms, each distinguished by
features such as group size and the reproductive roles of group
members. One focus in evolutionary biology is to identify the
causes of social behavior and its conspicuous variation, and to
determine the extent to which social organization is under
genetic control. Such information is useful for reconstructing
pathways of animal social evolution. Current views on insect
social evolution stress the importance of ecological and
behavioral environments in molding what are largely plastic
social behaviors.
... ... K.G. Ross and L. Keller (2 installations, US CH) report
evidence that major variation in the social organization of fire
ant colonies is under simple genetic control, providing a
demonstration of an apparent strong genetic component to complex
social behavior. The authors report that a single genomic element
(the gene [Gp-9]) is responsible for the existence of two
distinct forms of social organization in the fire ant *Solenopsis
invicta. This genetic factor apparently influences the
reproductive *phenotypes and behavioral strategies of ant queens
and determines whether workers tolerate a single fertile queen or
multiple queens per colony. The authors suggest "these findings
reveal how a single genetic factor can have major effects on
complex social behavior and influence the nature of social
organization."
-----------
K.G. Ross and L. Keller: Genetic control of social organization
in an ant.
(Proc. Natl. Acad. Sci. US 24 Nov 98 95:14232)
QY: Kenneth G. Ross: kenross@arches.uga.edu
-----------
Text Notes:
... ... *Solenopsis invicta: The fire ant S. invicta is an
introduced pest species in the southern US, the species existing
in two distinct social forms. The "monogyne" form features
colonies with a single fertile (egg-laying) queen, whereas the
"polygyne" form features colonies with multiple fertile queens.
The two social forms differ in other major aspects of their
reproductive biology.
... ... *phenotypes: The term "phenotype" refers to the total
appearance of an organism as determined by the interaction during
development between its genetic constitution (genotype) and the
environment.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 15Jan99
-------------------
Related Background:
ON HONEYBEE SOCIAL BEHAVIOR, GENES, AND THE ENVIRONMENT
The so-called social insects live in societies that rival human
societies in complexity and internal cohesion. Honey bees, for
example, apparently always follow 3 rules: a) they live in
colonies with overlapping generations; b) they care cooperatively
for offspring other than their own; and, c) they maintain a
reproductive division of labor. ... ... In a review of research
(much of it from the author's own laboratory) concerning the
genetic and environmental factors responsible for honey bee
behavior, Gene E. Robinson (University of Illinois Urbana-
Champaign, US) makes the following points: 1) Genes do not play
an exclusive role in regulating behavior: biologists have long
realized that behavior is influenced by genes, the environment,
and interactions between the two. 2) Genes never act alone. They
must operate in an environment where they code for proteins that
participate in many systems in an organism, with these systems in
turn influencing the expression of genes. Consequently,
biologists must take a broad approach in assessing the impact of
any gene. 3) The research group of the author uses the Western
honey bee, Apis mellifera. Honey bees pass through different life
stages as they age, and their behavioral responses to
environmental and social stimuli change in predictable ways.
Although worker bees go through a consistent path of behavioral
development, this path is not rigidly determined. Bees can
accelerate, retard, or even reverse their behavioral development
in response to changing environmental and colony conditions. 4)
Experimental evidence indicates that juvenile hormone, one of
the most important hormones influencing insect development, helps
time the pace of behavioral maturation in honey bees. The rate of
endocrine-mediated behavioral development is influenced by
inhibitory social interactions. Older bees inhibit the behavioral
development of younger bees: the rate of behavioral development
is negatively correlated with the proportion of older bees in a
colony. Inhibitory social interactions that influence the rate of
behavioral development involve chemical communication between
colony members. 5) Evidence from the laboratory of the author in
1993 indicated the so-called mushroom bodies in the bee brain are
involved in the behavioral changes occurring during maturation,
the volume of the bodies increasing, and the volume increase
associated with an increase in synapses with neurons from brain
regions devoted to sensory input. The author suggests this was
the first report of brain plasticity in an invertebrate. 6) The
author suggests that, in general, two-way interactions between
the nervous system and the genome contribute fundamentally to the
control of social behavior. Information about social conditions
that is acquired by the nervous system is likely to induce
changes in genomic function that in turn produce adaptive
modifications of the structure and function of the nervous
system. 7) The author proposes a new research initiative called
"sociogenomics", defined as a "wide-ranging approach to identify
genes that influence social behavior, determining the influence
of these genes on underlying neural and endocrine mechanisms, and
exploring the effects of the environment -- particularly the
social environment -- on gene action."
-----------
QY: Gene E. Robinson, Dept. of Entomology, Univ. of Illinois
Urbana-Champaign 217-333-3090.
(American Scientist Sep/Oct 1998 86:456)
(Science-Week 11 Sep 98)
-------------------
Related Background:
IN FOCUS: ON SOCIOBIOLOGY
"Evolutionary theory itself has an appropriately zoocentric
core... But the zoocentric view can be extended too far into a
caricature often called the "nothing but" fallacy (humans are
"nothing but" animals). The simplistic accounts of human
sociobiology now flooding popular literature embody this
overextended version of zoocentrism. Sociobiology is not just any
statement that biology, genetics, and evolutionary theory have
something to do with human behavior. Sociobiology is a specific
theory about the nature of genetic and evolutionary input into
human behavior. It rests upon the view that natural selection is
a virtually omnipotent architect, constructing organisms part by
part as best solutions to problems of life in local environments.
It fragments organisms into "traits", explains their existence as
a set of best solutions, and argues that each trait is a product
of natural selection operating "for" the form or behavior in
question. Applied to humans, it must view _specific_ behaviors
(not just general potentials) as adaptations built by natural
selection and rooted in genetic determinants, for natural
selection is a theory of genetic change. Thus, we are presented
with unproved and unprovable speculations about the adaptive and
genetic basis of specific human behaviors: why some (or all)
people are aggressive, xenophobic, religious, acquisitive, or
homosexual. Zoocentrism is the primary fallacy of human
sociobiology, for this view of human behavior rests on the
argument that if the actions of "lower" animals with simple
nervous systems arise as genetic products of natural selection,
then human behavior should have a similar basis."
-----------
Stephen Jay Gould: _Hen's Teeth and Horse's Toes_
(W.W. Norton, New York 1983, p.243)
(Science-Week 14 May 99)
-------------------
Related Background:
IN FOCUS: ON THE EVOLUTION OF HUMAN BEHAVIOR
"The uniqueness of Man is not a matter of his structure. His body
and its functions are in general very similar to those of other
mammals -- that is why medicine can study in animals the
functions of, say, kidneys, of the heart, of eye and ear, even
the basic functions of the nerve cells, and extrapolate with
confidence. The uniqueness of Man is agreed to be a matter of
behavior. If it is to be reduced to structural characters, it is
the brain that is unique, that functions in a unique way. There
are of course links with other structural characteristics, but
attempts (made in the past) to reduce Man's behavioral uniqueness
to, say, the possession of hands, or to his upright posture, have
not been very convincing -- they have been too simplistic, too
one-sided. The way the biologist approaches this problem is based
on his knowledge of the fact of evolution. No informed person can
doubt any more that Man has evolved, slowly and very gradually,
from ancestors which were far more similar to other mammals than
Man is now. This means that everything Man is and does now must
have evolved, through a long series of minute evolutionary steps,
from what his animal ancestors were and did. Man has diverged
very gradually from monkey or ape-like stock to what he is now,
just as modern closely related animal species have diverged from
common stock... It has often been pointed out that Man, himself a
product of evolution of a type similar to that which has created
all other animal forms, namely adaptive hereditary change, has
now embarked on a new type of evolution, which Huxley calls
'psycho-social evolution'. I prefer the term 'cultural
evolution'. It is based on _accumulated_ transfer, by tradition,
from one generation to the next, of knowledge (or _phenotypic_)
behavior changes, i.e., changes acquired through individual
experience. Our culture is very different from that of Cro-Magnon
Man, but generally we may not have changed much -- most of our
modern attributes are due to the accumulation of transferred
knowledge. We differ from animals not merely in the extent of
what we can ourselves learn, but in the progressive (and steadily
accelerating) accumulation of experience through the
generations."
-----------
Niko Tinbergen: _The Animal in its World_
(George Allen & Unwin, London 1972)
-----------
[Editor's note: Nikolaas Tinbergen (1907-1988) was awarded the
Nobel Prize in Physiology and Medicine in 1973, and is considered
one of the founders of ethology, the objective study of animal
behavior. Although researchers who approach human behavior in
terms of the evolution of genes (e.g., sociobiologists) often
cite Tinbergen as one of their intellectual sources, the above
quoted passage illustrates that Tinbergen's view of human
behavior was otherwise: Tinbergen approached human behavior
primarily in terms of the evolution of culture, rather than in
terms of the evolution of genes. (The quoted passage is from a
lecture given by Tinbergen at Oxford University, 27 October
1964.)] (Science-Week 29 Sep 00)
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