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ScienceWeek
SCIENCE-WEEK - December 21, 2001 - Vol. 5 Number 51
An Email Research Digest Published Weekly Since 1997
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Section 1
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Contents of this Issue (Full reports in Section 2):
1. Phosphoryl Transfer and Phosphoesters
2. Charge Transfer in DNA
3. Solvation of Doubly Charged Metal Cations
4. On the Nature of Light
5. Neurobiology of Emotions and Feelings
6. Sodium Ion Channel Genes
7. Ornaments in Paleolithic Culture
8. Chromosome Partitioning in Bacteria
9. Effects of Hydration on Protein Electronic Structure
10. On Gender Differences Among Embryos
11. Oncotic Cell Death
12. On Amyloid Fibrils
13. PostDoctoral Fellowship Profiles:
Laboratory of Tallie Z. Baram at Univ. Calif. Irvine (US)
14. In Focus: On Weather in the Tropics
15. From PRAXIS: On the Influenza Pandemic of 1918
16. This Week in PRAXIS
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Section 2
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1. PHOSPHORYL TRANSFER AND PHOSPHOESTERS
M.A. Anderson et al (University of Wisconsin Madison, US) discuss
phosphoesters. Phosphoryl transfer is enormously important in
biological systems, and with the exception of water, adenosine
triphosphate (ATP) is easily the most important chemical on Earth
for animal life. Indeed, ATP supplies the energy for muscular
movement, neural activity, biosynthesis, and active transport.
The chemistry of phosphomonoesters and phosphodiesters has been
studied intensely for many years, and in 1955, Westheimer and
Bunton independently proposed a metaphosphate intermediate in the
hydrolysis of phosphomonoesters. But in 1989, Herschlag
demonstrated that while there is considerable metaphosphate-like
character in the transition state, the evidence is against
formation of a true metaphosphate intermediate in aqueous
solution. For phosphomonoesters, the kinetics, pH-rate profiles,
effect of metal ions, and reactivity have all been determined at
one time or another. Phosphodiesters, the most stable of the
phosphate esters, have also been studied extensively. Most of the
studies done on monoesters have been used to determine the
reaction mechanism of phosphodiester hydrolysis also. Both esters
have been studied enzymatically and such research has added
greatly to the understanding of the chemistry that takes place in
the active site of the protein. In contrast, the chemical
hydrolysis of triesters has not been studied as extensively as
that of the less ligated phosphoesters, primarily because there
are no naturally occurring phosphotriesters in nature.
Phosphotriesterase activity was discovered in the soil microbe
Pseudomonas diminuta in 1974, but the reason for the existence of
this enzyme remains a puzzle.
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J. Am. Chem. Soc. 2001 123:9246
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2. ON CHARGE TRANSFER IN DNA
S. Hess et al (Munich Technical University, DE) discuss charge
transfer in DNA. Charge migration phenomena in DNA are the
subject of intense current research, studies driven to a large
extent by the implication of electronic conduction in the
pathways of oxidative damage and also by implications for the
development of electrochemical biosensor and nanoelectronic
devices. In the early 1990s, intense interest in the field was
stimulated by the two conjectures of DNA as a "molecular wire"
exhibiting "chemistry at a distance". In fact, the molecular wire
concept is reminiscent of aromatic hydrocarbon crystals in which
two extreme modes of carrier transport can exist: a) excess
carriers may be delocalized, exhibiting a relatively large mean
free path; or b) excess carriers may be localized, for example,
in a potential well caused by a polarization of the lattice, and
consequently the carriers move in a thermally activated hopping
process. Independent of the type of carrier motion, chemical side
reactions of charge carriers can occur at surface sites which
correspond to the macroscopic dimensions of the crystal. As
applied to DNA, the idea of "chemistry at a distance" depends on
reactive intermediates, for example, oxidized guanines, which
effectively migrate from the site of generation to a distant site
of reaction. In the case of transport of positive charges
(holes), analyses of DNA strand cleavage patterns have
demonstrated that distances of approximately 200 angstroms can be
spanned in an almost distance-independent fashion. In contrast to
an aromatic crystal, the description of long-range hole transport
in the DNA duplex is complicated by the different energetics of
the nucleotide bases, that is, the different oxidation potentials
of guanine, adenine, thymine, and cytosine.
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J. Am. Chem. Soc. 2001 123:10046
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3. ON THE SOLVATION OF DOUBLY CHARGED METAL CATIONS
A.A. Shvartsburg and K.W. Siu (York University, CA) discuss the
solvation of doubly charged cations. The study of ion solvation
has been among the classical pursuits in physical chemistry since
its early beginnings. Solvation of multiply-charged metal ions is
of special interest because of the rich chemistry often
associated with it, a chemistry involving charge transfer and
formation of specific well-defined complexes and solvation
shells. A recent new perspective is that similar patterns may be
exhibited in the coordination of metal ion hemes in proteins and
other biological molecules ("self-solvation"), and this aspect
attracts further attention to the solvation of metal ions in
finite systems. These processes can be investigated by mass
spectrometry, which allows one to clearly elucidate the
thermodynamics and other properties of stepwise solvation.
Another major advantage of finite systems is that close
connection with reasonably accurate theory can be made. However,
dissociative charge transfer has for a long time limited the
research on solvated metal ions to singly-charged ions. Indeed,
the second ionization potentials of metal atoms are, with few
exceptions, above 12 electronvolts, while the first ionization
potentials of most common solvent molecules lie in the 9 to 12
electronvolt range (e.g., 12.6 eV for water). Thus, electron
transfer from a neutral ligand to a multiply-ionized metal atom
is typically energetically favorable and should occur
spontaneously on contact, with the dissociation (in water, for
example) driven by Coulomb repulsion to yield a singly-charged
cation plus a positively charged water molecule. The result is
that, depending on which doubly-charged cation and which solvent
are involved, stepwise solvation may not occur at all.
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J. Am. Chem. Soc. 2001 123:10071
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4. ON THE NATURE OF LIGHT
T. Brown et al (University of St. Andrews, UK) discuss the nature
of light. What is light? This question might at first sight seem
an odd one to ask -- light is all around us and generally taken
for granted. But any attempt to really get to grips with the
nature of light takes one on a fascinating journey into the heart
of physics. Light can be thought of as a wave consisting of very
fast oscillations of an electric field. A typical light wave may
have a wavelength of 800 x 10^(-9) meters, which, bearing in mind
the speed of light [3 x 10^(8) meters per second], gives a
frequency for the wave of 3.75 x 10^(14) hertz. This means that
one cycle of the electric field in the light wave takes place in
just 2.7 x 10^(-15) seconds, or 2.7 femtoseconds. In most
situations, this fast variation in the electric field is too
rapid to be noticed, and what is observed rather is the envelope
function that modulates the underlying fast carrier variation.
Laser systems provide the ideal tool to investigate the
properties of light. The light beams produced by a laser are
"coherent"; that is, a fixed phase relationship exists in the
output, in contrast to light encountered in every day life. Some
modern laser systems are designed to produce light in the form of
very short and regularly spaced pulses rather than in the more
familiar continuous wave or "always-on" format. The pulse
periodicity is governed by the physical size of the laser, and
the output is a sequence of abrupt short pulses. The pulse
duration is short compared with the pulse repetition rate, and
the average power from such systems is thus relatively low, but
the peak power of the pulses is several orders of magnitude
higher.
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Science 2001 293:1265
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SCIENCE-WEEK 21 Dec 2001 http://scienceweek.com
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Related Background:
EXPERIMENTAL PHYSICS: FIRST EFFECTIVE ZERO-VELOCITY LIGHT
Experiments involving the control of light pulses in a quantum
mechanical regime hold great promise for a future technology of
quantum computing involving optical information storage and
transmission. In 1999, L.V. Hau et al succeeded in slowing light
to a velocity of 30 meters per second in an ultracold sodium gas.
Now the same laboratory reports effectively stopping light
completely for an interval of 1 millisecond before releasing the
pulse to resume normal velocity. Essentially, the phenomenon
involves "storing" the light pulse in the quantum states of the
atoms, with the light pulse reconstituted for propagation at a
later time.
... ... C. Liu et al (4 authors at 2 installations, US) report
observations of halted light pulses, the authors making the
following points:
1) The authors point out that "*electromagnetically induced
transparency" is a quantum interference effect that permits the
propagation of light through an otherwise opaque atomic medium. A
"coupling laser" is used to create the interference necessary to
allow the transmission of resonant pulses from a "probe laser".
This technique has previously been used to slow and spatially
compress light pulses by 7 orders of magnitude, resulting in
their complete localization and containment within an atomic
cloud.
2) The authors report the use of electromagnetically induced
transparency to bring laser pulses to a complete stop in a
magnetically trapped cold cloud of sodium atoms (approximately 11
million sodium atoms at 0.9 microkelvins). Within the spatially
localized pulse region, the atoms are in a *superposition state
determined by the amplitude and phases of the coupling and probe
laser fields. Upon sudden turn-off of the coupling laser, the
compressed probe pulse is effectively stopped, and *coherence
information initially contained in the laser fields is "frozen"
in the atomic medium for up to 1 millisecond. When the coupling
laser is turned back on, the probe pulse is regenerated: the
stored coherence is read out and transferred back into the
radiation field. The authors present a theoretical model from
which it is concluded that the system is self-adjusting to
minimize dissipative loss during the "read" and "write"
operations. The authors state: "We anticipate applications of
this phenomenon for quantum information processing."
... ... In a commentary on this work, Eric A. Cornell (University
of Colorado, US) states: "The key fact here is that as the pulse
of light penetrates into the dense region of the ultracold atomic
cloud, it turns into a "quantum coherence pattern" printed on the
sodium atoms -- the information in the light beam becomes stored
in the quantum phase relationships within the internal atom
states. In the final limit, when the pulse comes to a dead stop,
all the photons have been "imprinted" (absorbed in a fully
reversible way) into the coherence pattern. Later, when the
coupling light is turned back on, the information contained in
the pattern is read out and converted back into propagating
photons that accelerate to the conventional speed of light as
they come to the edge of the atom sample."
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Nature 25 Jan 01 409:461,490
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Notes:
... ... *electromagnetically induced transparency: In his
commentary, Cornell states: "The key to slowing light is the
presence of a second laser beam, the so-called 'coupling' pulse.
Distinguishable from the propagating (or 'probe') pulse by its
polarization, the coupling light delicately adjusts the internal
energy levels of the atoms, suppressing their ability to absorb
the probe light -- in effect, a single absorption level is split
into two levels that cancel each other out. This phenomenon is
known as 'electromagnetically induced transparency'.
... ... *superposition state: In this context, the general idea
is that the cloud of sodium atoms (335 microns by 55 microns in
this experiment), under these laser conditions, behaves almost as
a single quantum mechanical entity: the quantum states of the
atoms are superposed into a single wave function for the entire
system.
... ... *coherence information: In quantum physics, coherence
involves the locking of phase differences between wave functions:
the wave functions of two or more particles are said to be
coherent if the phase difference between their wave functions
remains constant. In general, a perfectly coherent system of
particles can be described by a single macroscopic wave function.
In general, in optics, the term "coherence" refers to the
existence of a correlation between the phases of two or more
waves. In this context, the term "coherence information" refers
to information contained in and dependent upon the coherence of
the laser pulse.
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Summary & Notes by SCIENCE-WEEK http://scienceweek.com 16Feb01
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SCIENCE-WEEK 21 Dec 2001 http://scienceweek.com
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Related Background:
IN FOCUS: ON THE HISTORY OF THE PHYSICS OF LIGHT
"The revival of the wave theory of light, begun by Thomas Young
(1773-1829), is one of the most important features of the history
of the 19th century. Young pointed out that the dividing of a
beam of light into a refracted ray at the interface between two
mediums was to be expected from the wave theory but had not been
satisfactorily explained on the corpuscular theory. In 1801, he
presented to the Royal Society a paper 'On the Theory of Light
and Colors', in which he proposed the principle of the
interference of two wave trains as an explanation of Newton's
rings and the colors of thin plates. From Newton's measurements
of the thickness of the air layers necessary to produce the
several colors, Young was enabled to compute wavelengths. In
subsequent papers, he described the interference fringes which he
had observed by placing hairs on silk threads in front of a
narrow slit illuminated from the rear; he announced the change of
phase on reflection; he explained diffraction bands by the
principle of interference; and he showed that the spacing of
these bands gave values of the wavelength agreeing with those
obtained from Newton's rings and that, therefore, both phenomena
must be due to a common cause... But the dogmatic spirit in
regard to scientific matters was not yet dead. Young's paper
aroused a storm of protest, even of derision and abuse. He was
attacked not by the church, as was Galileo, but by some of his
scientific, or, more probably, pseudoscientific contemporaries.
His chief assailant was Henry Brougham, afterward Lord Chancellor
of England, who 'reviewed' Young's papers in the _Edinburgh
Review_. The nature of Brougham's attack is indicated by the
following quotation: 'We wish to raise our feeble voice against
innovations that can have no other effect than to check the
progress of science and renew all those wild phantoms of the
imagination which Bacon and Newton put to flight from her temple.
We wish to recall philosophers to the strict and severe methods
of investigation.' Although Young replied at length in a
privately published pamphlet, it was a long time before public
opinion was willing to receive his theories with an open mind."
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F.K. Richtmyer et al: Introduction to Modern Physics (5th ed.)
(McGraw-Hill, New York 1955, p.33)
[Editor's note: Thomas Young (1773-1829) was an infant prodigy
who matured into an adult prodigy. At Cambridge, he was called
"Phenomenon Young". He studied and practiced medicine, but failed
at it because of the apparent absence of a "suave bedside
manner". But while still a medical student, he was the first to
discover the manner in which the lens of the eye changes shape
(accommodation) in focusing on objects at differing distances.
And it was Thomas Young who, in 1801, explained astigmatism as
resulting from irregularities in the curvature of the cornea. The
early rejection of Young's wave theory of light by his British
contemporaries was due more to chauvinism than to reason: the
particle theory of light was essentially British; the wave theory
of light was essentially French. At the age of 41, Young
abandoned both medicine and physics and devoted himself to an
analysis of the Rosetta Stone. In 1818, he produced a classic
paper on Egypt that laid the groundwork for the later definitive
analysis of the Rosetta Stone by Jean Francois Champollion (1790-
1832).]
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ScienceWeek 2001 26 Jan
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Related Background:
EXPERIMENTAL PHYSICS:
ON EXCEEDING THE VELOCITY OF LIGHT
The term "absolute refractive index" (refractive constant)
refers to the ratio of the speed of electromagnetic radiation in
free space to the speed of the radiation in a particular medium,
with the refractive index varying with the wavelength of the
radiation. (The term "relative refractive index" refers to ratio
of the speed of electromagnetic radiation in one medium to that
in an adjacent medium.)
In general, the term "dispersion" refers to the
decomposition of a beam of white light into colored beams that
spread out to produce a spectrum. More specifically, dispersion
is concerned with descriptions of the variation of refractive
index with wavelength.
Ordinary (normal) dispersion is exhibited by most
transparent substances, which show increasing refractive index
with decreasing wavelength, the variation being greater at
shorter wavelengths.
The term "anomalous dispersion" refers to marked changes in
the curve relating refractive index to wavelength when the
wavelength is near the absorption bands of the material. On the
longer wavelength side of the absorption band, the refractive
index is high; on the shorter wavelength side of the absorption
band, the refractive index is low. Hence, the adjective
"anomalous".
An experimental "light pulse" has a finite duration, and in
theory (the so-called "bandwidth theorem") this requires an
infinite number of waves of different frequency to be added
together. The shorter the desired pulse, the larger the bandwidth
of frequencies that must be used. Theoretically, all light pulses
are therefore formed by a packet of waves of different frequency,
each of which has a different amplitude and phase. The speed of
individual waves is called the "phase velocity", and the velocity
at which the peak of the wave packet propagates is called the
"group velocity". In a vacuum, the phase and group velocities are
identical, but in a highly absorbing or dispersive medium the
phase and group velocities are usually different. A so-called
"negative group velocity" results when the phases of the
different frequency components are shifted by the medium through
which they travel in a way such that the wave packet they form at
the exit is brought forward in time compared with the same pulse
traveling through a vacuum.
During the past two decades, using various techniques,
researchers have demonstrated the transmission of certain light
pulses over short distances with apparent velocities greater than
the speed of light (c =~ 3 x 10^(8) meters per second) in a
vacuum, the effect known as "superluminal light propagation". The
experimental conditions are extremely specific, and the results
difficult of general interpretation. But despite ballyhoo in the
popular media concerning these experiments, the rule in physics
remains intact: no mass can travel faster than (c), and no
information or signal can be transmitted faster than (c). Any
violation of this rule would imply a violation of both Einstein's
theory of special relativity and the principle of causality --
and the rule has not yet been demonstrated to be violated
anywhere.
... ... L.J. Wang et al (3 authors at NEC Research Institute, US)
present a report of experiments on superluminal light
propagation, the authors making the following points:
1) The authors report the use of gain-assisted linear
anomalous dispersion to demonstrate superluminal light
propagation in atomic cesium gas, with the group velocity of a
laser pulse of wavelength near the absorption line of the medium
exceeding (c) and even becoming negative, while the shape of the
pulse is preserved. The authors report they measured a group
velocity index of -310(+-5), which in practice "means that a
light pulse propagating through the atomic vapor cell appears at
the exit side so much earlier than if it had propagated the same
distance in a vacuum, that the peak of the pulse appears to leave
the cell before entering it." The authors suggest the observed
superluminal light pulse propagation is not at odds with
causality, since it is "a direct consequence of classical
interference between its different frequency components in an
anomalous dispersion region [of the curve relating refractive
index to wavelength]."
2) In a commentary on this work in the same journal, Jon
Marangos (Imperial College London, UK) states: "Traditionally,
the signal velocity of a light pulse is defined as the speed at
which the half peak-intensity point on the rising edge of the
waveform travels; in [the Wang et al] experiment, this is clearly
superluminal. In contrast, some researchers argue that the true
speed at which information is carried by a light pulse is not the
group velocity of a smooth pulse, but rather the speed at which a
sudden step-like feature in the waveform travels, which so far
has not been shown to exceed (c)."
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Nature 20 Jul 00 406:243,277
SCIENCE-WEEK 2000 4 Aug
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5. ON THE NEUROBIOLOGY OF EMOTIONS AND FEELINGS
Antonio Damasio (University of Iowa, US) discusses the biological
basis of emotions, the author making the following points:
1) The groundwork for the science of emotions was laid down
over 100 years ago, but neuroscience has for the most part
avoided the problem until recently. It is not usually appreciated
that the probable cause of the neglect of the topic was the
improper distinction between the concepts of emotion and
feelings.
2) Some traits of feelings -- their subjective nature, the
fact that they are private, hidden from view, and often difficult
to analyze -- were in the past projected onto emotions, so that
emotions too were deemed subjective, private, hidden, and
elusive. This conflation of the two concepts persists, as does
the idea that the neurobiology of feelings is out of reach.
3) An emotion, be it happiness or sadness, embarrassment or
pride, is a patterned collection of chemical and neural responses
produced by the brain when it detects the presence of an
emotionally competent stimulus -- an object or situation, for
example. The processing of the stimulus may be conscious, but it
need not be, as the responses are engendered automatically.
4) The main target of an emotional response is the body --
the "internal milieu", the viscera and the musculoskeletal system
-- but there are also identifiable targets within the brain
itself. The result of the body-targeting responses is the
creation of an emotional state -- involving adjustments in
homeostatic balance -- as well as the enactment of specific
behaviors, such as freezing or fight-or-flight, and the
production of particular facial expressions.
5) A working definition of "feelings" is a different matter.
Feelings are the mental representation of the physiological
changes that characterize emotions. Because feelings are the
direct consequences of emotions, the elucidation of emotional
neurobiology opens the way to elucidating the neurobiology of
feelings.
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Nature 2001 413:781
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Related Background:
NEUROSCIENCE: NATURE OF HUMAN EMOTIONS
Although what we call "emotions" certainly involve
significant events in the nervous system, and neural structures
strongly associated with emotions have been identified, most
advanced textbooks in neuroscience devote only minor space to
emotions, and some textbooks avoid the subject completely. There
are many reasons for this, and one reason is that despite the
scientific attention given to emotions by the archetypical
classical biologist Charles Darwin, human emotions (grouped as
"affect") are traditionally considered the investigative province
of psychology and psychiatry rather than a province of
neurobiology. But this attitude is rapidly changing. We certainly
know more now about the neurobiological correlates of emotions
than we did 50 years ago, and new techniques are making possible
important new research.
In general, all emotions are expressed through both
physiological changes and stereotyped motor responses, especially
responses of the facial muscles. These responses accompany
subjective experiences that although not easily described are
apparently much the same in all human cultures. Expression of the
emotions is closely tied to the autonomic nervous system, and it
therefore involves the activity of certain defined brain
structures (e.g., brainstem nuclei, hypothalamus, amygdala), as
well as autonomic nervous system components (e.g., preganglionic
neurons in the spinal cord, autonomic ganglia, peripheral
effectors). The brain centers that coordinate emotional responses
have been grouped as the "limbic system". At the level of the
cerebral cortex, the two hemispheres apparently differ in their
governance of the emotions, with the right hemisphere more
critically involved than the left hemisphere.
... ... Robert Plutchik (Albert Einstein College of Medicine, US)
presents a review of current ideas concerning the nature of human
emotions, the author making the following points:
1) The author points out that what we call "cognition" --
the activity of knowing, learning, and thinking, of which emotion
is a part -- evolved over millions of years. Charles Darwin
(1809-1882) recognized that the process of evolution by natural
selection applied not only to anatomic structures but also to the
"mind" of an animal and to expressive behavior, a conclusion that
led him to write a treatise on emotional expression (_The
Expression of Emotion in Man and Animals_, 1872). Those who have
followed Darwin in studying the evolutionary origins of emotions
have sought to understand how emotions increase evolutionary
fitness for the individual.
2) The author points out that an emotion is not simply a
feeling state: emotion is a complex chain of loosely connected
events, the chain beginning with a stimulus and including
feelings, psychological changes, impulses to action, and specific
goal-directed behavior. In other words, feelings do not happen in
isolation. They are responses to significant situations in the
life of an individual, and often they motivate actions. The
author suggests this definition of emotions allows the concept to
be generalized to lower animals without difficulty. From his
studies of animals, human infants, and human adults, Darwin
concluded that expressive behaviors communicate information from
one animal to another about what is likely to happen, and
emotions therefore affect the chances of survival of the
individual demonstrating the behavior. Darwin stated: "Even
insects express anger, terror, jealousy, and love by their
stridulations."
3) The author (Plutchik) proposes that in general emotions
are activated in an individual when issues of survival are raised
in fact or by implication. Such situations include threats,
attacks, poisonous substances, or the sighting of a potential
mate. The effect of the emotional state is to create an
interaction between the individual and the event or stimulus that
precipitated the emotion. The interaction usually takes the form
of an attempt to reduce the disequilibrium and reestablish a
state of comparative rest.
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American Scientist 2001 89:344
SCIENCE-WEEK 2001 3 Aug
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Related Background:
NEUROBIOLOGY: ON THE BRAIN AND VIOLENCE
Although human violence has been a major focus of research
in psychiatry, psychology, and the social sciences,
neurobiological studies of human violence have been relatively
uncommon. Neurobiology, however, is a major component in our
understanding of human behavior: genetics, environment, brain
structure and brain function are all involved in both ordinary
behavior and in violent behavior.
... ... C.M. Filley et al (3 authors at 3 installations, US)
present a commentary on current research on violence and the
human brain, the authors making the following points:
1) The authors point out that in adults, the role of brain
damage in violence remains unclear. A brain lesion by itself is
rarely sufficient to cause violent behavior, and most individuals
with brain damage do not commit criminal acts. But we cannot
assume that the brains of violent individuals are invariably
normal. The neurologic status of the brains of violent persons
has not been adequately assessed by detailed neurological
examination, neuropsychological testing, *magnetic resonance
imaging, or *functional neuroimaging. Studies of murderers have
suggested a high prevalence of neurologic dysfunction, and some
individuals with traumatic brain injury, epilepsy, dementia, and
sleep disorders have been observed to exhibit excessive violence.
Violence is more likely among those with severe mental illness,
particularly psychosis, and violence is exacerbated by the use of
alcohol and other psychoactive substances.
2) The authors point out that detailed analysis of the
neurobehavioral aspects of violence is complex:
... ... a) The cause of violence is multifactorial, and a direct
correlation between brain dysfunction and a violent act is rarely
possible.
... ... b) Identification of brain lesions is imperfect given the
limitations of diagnostic classifications, the limitations of the
neurologic examination, the limitations of neuroimaging
technologies, the limitations of neuropsychological assessment,
and the limitations of neurochemical analysis.
... ... c) Some subject samples, such as prisoners or those with
severe neurologic or psychiatric disease, are necessarily based
on violent persons who are apprehended or hospitalized.
Conclusions are therefore based only on those whose records are
analyzed, and the potential for violence in the general
population remains unknown.
3) There is the possibility of a neurogenetic contribution
to violent behavior. Although no single gene for human violence
has been discovered, data from molecular genetics indicate that
multiple genes may interact to predispose individuals to violent
behavior. Observations in mouse *knockout models have suggested
that targeted disruption of single genes can induce
aggressiveness in males and diminish nurturing in females.
Aggression in animals and humans is also likely related to genes
regulating central nervous system *serotonin metabolism.
4) In general, males are much more likely to commit violent
acts than are females, but genetic factors may not explain this
discrepancy. Socioeconomic and cultural influences play a major
role. Unemployment, lower educational level, alcohol abuse, and
access to firearms all contribute to violent crime among males.
The *XYY chromosomal disorder serves to highlight difficulties in
establishing an influence of gender on violence.
5) Although no "violence center" exists in the brain, the
*limbic system and the *frontal lobes are areas most implicated
in violence. The limbic system is the neuroanatomic substrate for
many aspects of emotion. The limbic system structure most often
implicated in violent behavior is the *amygdala: placidity has
been described in humans with bilateral amygdala damage, whereas
violence has been observed in those with abnormal electrical
activity in the amygdala. The frontal lobes are apparently the
areas of the most advanced functions of the brain. In particular,
the *orbitofrontal cortices are involved in the inhibition of
aggression: individuals with orbitofrontal injury have been found
to display antisocial traits that justify the diagnosis of
"acquired sociopathy", and some of these individuals have an
increased risk of violent behavior. A balance apparently exists
between the potential for impulsive aggression mediated by limbic
structures, and the control of this drive by the influence of the
orbitofrontal regions.
6) The authors conclude: "Whereas dysfunction of a discrete
brain region, isolated neurochemical system, or single gene will
not likely emerge as a direct cause of violence, all may
contribute."
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The Scientist 2001 2 Apr
-----------
Notes:
... ... *magnetic resonance imaging: Magnetic resonance imaging
(MRI) is essentially a technique for examining morphology (as
opposed to _functional_ magnetic resonance imaging, which is a
technique for examining anatomical correlates of function). In
general, MRI involves magnetic coils producing a static magnetic
field parallel to the long axis of the patient or subject,
combined with inner concentric magnetic coils producing a static
magnetic field perpendicular to the long axis. A radio-frequency
coil specifically designed for the head perturbs the static
fields to generate a magnetic resonance image. The interaction
physics in this technique is that between the magnetic fields and
atomic nuclei in brain tissue. "Sliced" views can be obtained
from any angle, and the resolution is quite high and on the order
of millimeters for magnetic field strengths of 1.5 tesla.
... ... *functional neuroimaging: Functional magnetic resonance
imaging (fMRI) is based on the fact that oxyhemoglobin, the
oxygen-carrying form of hemoglobin, has a different magnetic
resonance signal than deoxyhemoglobin, the oxygen-depleted form
of hemoglobin. Activated brain areas utilize more oxygen, which
transiently decreases the levels of oxyhemoglobin and increases
the levels of deoxyhemoglobin, and within seconds the brain
microvasculature responds to the local change by increasing the
flow of oxygen-rich blood into the active area. This local
response thus leads to an increase in the oxyhemoglobin-
deoxyhemoglobin ratio, which forms the basis for the fMRI signal
in this technique. Because of its high spatial resolution
(millimeters) and high temporal resolution (seconds) compared to
other imaging techniques, fMRI is now the technology of choice
for studies of the functional architecture of the human brain.
Positron emission (PET) tomography is a technique for producing
cross-sectional images of the body after ingestion and systemic
distribution of safely metabolized positron-emitting agents. The
images are essentially functional or metabolic, since the
ingested agents are metabolized in various tissues.
Fluoro-deoxyglucose and H(sub2)O(sup15) are common agents used
for cerebral applications, and in cerebral applications of
central importance to the technique is the fact that changes in
the cellular activity of the brains of normal, awake humans and
unanesthetized laboratory animals are invariably accompanied by
changes in local blood flow and also changes in oxygen
consumption.
... ... *knockout models: In general, in this context,
"knockout technology" involves the generation of a mutant
organism (usually a mouse) with a missing specific gene.
... ... *serotonin metabolism: A neurotransmitter substance
involved in nearly everything occurring in the brain, including
psychological states such as anxiety and depression, and
dysfunctions producing migraine and epilepsy.
... ... *XYY chromosomal disorder: Humans ordinarily have 46
chromosomes. Of this number, 44 are not sex-related and are
called "autosomal". Two chromosomes, X and Y, are sex-related. An
individual with two X chromosomes is a female; an individual with
one X and one Y chromosome is a male. Approximately 1 in 1000
males have an extra Y chromosome (total 47 chromosomes), and this
abnormality is denoted as "47,XYY". Such individuals are often
characterized by tallness, severe acne, and sometimes skeletal
malformations and mental deficiency. It has been suggested that
the presence of an extra Y chromosome in an individual may cause
him to be more aggressive and prone to criminal behavior, but
recent studies of the general population have cast doubt on the
validity of this linkage.
... ... *limbic system: In general, this refers to those cortical
and subcortical structures ("cortical" refers to cerebral cortex)
concerned with the emotions. The most prominent anatomical
components of the limbic system are the cingulate gyrus, the
hippocampus, and the amygdala, all "deep brain" structures and
not visible on the exterior surface of the brain.
... ... *frontal lobes: One of the four lobes of the brain. The
other lobes are the parietal lobe, the temporal lobe, and the
occipital lobe. Each hemisphere has these 4 lobes.
... ... *amygdala: A cellular complex in the temporal lobe that
forms part of the limbic system. The major functional correlates
of the amygdala are autonomic nervous system behavior, emotional
behavior, and sexual behavior.
... ... *orbitofrontal cortices: The orbitofrontal cortex lies
directly under the forehead skull.
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SCIENCE-WEEK 2001 13 Apr
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SCIENCE-WEEK 21 Dec 2001 http://scienceweek.com
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6. ON SODIUM ION CHANNEL GENES
G.F. Lopreato (University of Texas Austin, US) discuss sodium ion
channel genes. The evolution of voltage-dependent sodium ion
channels in metazoans permitted long-distance propagation of
action potentials. For many years this was still believed to be
the main function of such channels, but recently it has been
demonstrated that sodium ion currents participate in shaping and
filtering synaptic inputs, back-propagation of dendritic action
potentials (which can have enormous consequences for associative
synaptic plasticity), and initiation and maintenance of cellular
oscillations and burst generation. Sodium ion currents also have
been implicated in various forms of developmental and regulatory
plasticity. Last, sodium ion channels are the locus of a number
of mutations resulting in a variety of muscle, cardiac, and
neural diseases. Sodium ion channel genes have been cloned and
sequenced in a number of phyla, and an interesting pattern has
emerged: whereas only a single or a few sodium ion channel genes
are reported in invertebrate species, 10 distinct sodium ion
channel genes have been identified in mammals. Various methods
have revealed cell-specific expression and subcellular
localization of many of these mammalian sodium ion channels,
leading to a more complex picture of sodium ion channel function
in the mammalian brain. When in evolution this proliferation of
sodium ion channel genes and the differential localization of
their products occurred remains unknown. In humans, all 10 sodium
ion channel genes reside on 4 chromosomes with clusters of 3 and
5 sodium ion channel genes respectively on human chromosomes 3
and 2.
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Proc. Nat. Acad. Sci. 2001 98:7588
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7. ON ORNAMENTS IN PALEOLITHIC CULTURE
S.L. Kuhn et al (University of Arizona, US) discuss the use of
ornaments in the Paleolithic era. Today, the practice of
decorating oneself with pigment or objects is universal among
human cultures, such that most of us take personal ornaments for
granted. Nonetheless, the appearance of ornaments such as beads
and pendants during the Paleolithic era marks an important
rubicon in the evolution of human behavior. Such objects are
among the first documentable forms of information technology, the
earliest unambiguous use of material objects as media for
communication. Widespread use of comparatively standard ornament
forms such as beads and pendants of shell, tooth, ivory, or stone
is a hallmark of the Upper Paleolithic era, a series of
archeological techno-complexes that appeared around or shortly
after 45,000 years ago in Eurasia. Ornament-making traditions are
also characteristic of the Late Stone Age, the African equivalent
of the Upper Paleolithic. The Upper Paleolithic can no longer be
considered exclusively the product of anatomically modern humans,
at least in Europe, but the proliferation of the Upper
Paleolithic does coincide with the radiation of modern humans
within Eurasia and the eventual disappearance of the
Neanderthals. Ornaments have occasionally been reported from
archeological deposits containing late Middle Paleolithic or
Middle Stone Age chipped stone artifacts, but questions persist
as to whether these rare objects are actually artifacts or were
introduced into Middle Paleolithic layers by subsequent
disturbance of sediments. The authors report new data from sites
on the northern Levantine coast, the data interpreted as
demonstrating that the initial appearance of Upper Paleolithic
ornament technologies was essentially simultaneous on three
continents and appears to have been contingent on variable
demographic or social conditions. If parallels can be drawn with
recent human societies, beads and pendants may have been used in
the Upper Paleolithic/Late Stone Age to communicate social
identity, such as group membership, gender, and individual life-
history characteristics (age, marital status, etc.).
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Proc. Nat. Acad. Sci. 2001 98:7641
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8. ON CHROMOSOME PARTITIONING IN BACTERIA
K.P. Lemon and A.D. Grossman (Harvard University, US) discuss
chromosome partitioning. Successful cellular reproduction
requires accurate duplication and partitioning (segregation) of
sister genomes produced by mitosis, and failure to correctly
partition the sister genomes results in aneuploidy. The
consequences of these errors range from loss of normal cellular
function (e.g., loss of normal growth controls in tumor cells) to
cell death. In prokaryotes with a single chromosome, partitioning
failures are fatal for at least one of the two daughter cells: a
so-called "anucleate cell" forms when one daughter receives no
chromosome and the other daughter receives two chromosomes.
Several findings in recent years have fundamentally altered our
views of chromosome partitioning in prokaryotes, the flurry of
new observation ignited by adaptation of various cell biological
techniques used in studies of eukaryotes for use in prokaryotes.
In chromosome partitioning in bacteria that have a single
circular chromosome, DNA replication initiates once per cell
division cycle from a specific chromosomal locus (oriC) and
proceeds bidirectionally to terminate in a defined region
opposite the origin (terC). The basic components of the DNA
replication machinery are highly conserved in bacteria. In fact,
these basic components are functionally conserved from bacteria
to mammals. However, fundamental differences exist between
chromosome partitioning in eukaryotes and prokaryotes. In
contrast to the temporal separation of chromosome replication and
partitioning in eukaryotes, regions of the bacterial chromosome,
starting with the origin, appear to be partitioned soon after
duplication, whereas the remainder of the chromosome awaits
replication. In general, in bacteria, DNA replication, chromosome
refolding, and chromosome partitioning are concurrent, while in
eukaryotes, these processes are generally sequential. There is no
evidence that bacteria contain eukaryotic-like mitotic spindles
or mitotic motors.
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Genes and Dev. 2001 15:2031
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SCIENCE-WEEK 21 Dec 2001 http://scienceweek.com
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9. EFFECTS OF HYDRATION ON PROTEIN ELECTRONIC STRUCTURE
K. Ohno et al (Tokyo Institute of Technology, JP) discuss
hydration and protein electronic structures. Water constitutes 70
to 90 percent of the mass in most living systems, and water plays
an important role in maintaining structure and function in
proteins. The so-called "hydrophobic interaction" arises from
interactions of nonpolar moieties, leading to a marginal
stability of the native structure of a protein relative to the
denatured state. In addition to such a conventional picture of
protein structure, new aspects of the role of hydration in
protein chemistry have been revealed by recent quantum-chemical
studies. For example, a significant amount of charge transfer has
been found to occur between a protein and surrounding water
molecules. This changes the electronic structure of the protein-
water interface and may affect the stability of the protein-
substrate complex when the protein is an enzyme. Recent
development of molecular orbital methods has extended the realm
of quantum-chemical calculation to clarify the electronic
structure of hydrated proteins. Unlike charge transfer, the
polarization of a solvent is expected to exert its influence on
almost all residues because of the long range nature of
polarization effects. The authors report their molecular orbital
calculations indicate that hydration causes a large modification
of the energy and spatial distributions of the molecular orbitals
of the protein, and that the frontier orbitals of the hydrated
protein are found to be localized on several functionally
important residues.
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J. Am. Chem. Soc. 2001 123:8161
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10. ON GENDER DIFFERENCES AMONG EMBRYOS
M.A. Larson et al (Stowers Institute for Medical Research, US)
discuss differences in embryos. Gender differences among embryos
can be detected well before the gonads begin to form. The most
frequently reported example is in the relative rates of cleavage
of male and female embryos in the first few days after
fertilization. Embryos produced in vitro in a number of species
fall into fast-cleaving and slow-cleaving groups, which are
predominantly male and female, respectively. This phenomenon has
been observed for bovine, mouse, sheep, and human embryos. In
vivo-produced male pig embryos, both before and subsequent to
hatching from the zona pellucida, have also been reported to be
larger and to have more cells than female embryos. That male
embryos develop faster than female embryos is by no means
universally accepted, however. Some studies have reported no
differences in human and bovine embryos. Similarly, male and
female pig embryos have been estimated to grow at similar rates
in utero. There are at least three mutually exclusive
explanations for these contrasting observations: 1) a genetic
effect resulting from the use of different breeds or strains; 2)
in cases of in vitro culture, the culture conditions influence
the outcome; 3) the manner in which growth rates are measured.
The authors provide experimental evidence that in vitro-produced
male bovine embryos do not have an inherently faster rate of
growth than females.
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Proc. Nat. Acad. Sci. 2001 98:9677
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11. ONCOTIC CELL DEATH
F. Ma et al (Harvard University, US) discuss oncosis. The
importance of cell death is demonstrated by the fact that
dysregulation of cell death can lead to cancer, developmental
abnormalities, and autoimmune disorders. Both cell
proliferation/differentiation and cell death are equally
important for maintaining proper homeostasis. Tremendous progress
in our understanding of a particular form of cell death,
"apoptosis", has been made following the molecular cloning of
various cell death receptors. Engagement of these receptors by
their ligands or by specific antibodies is known to initiate the
activation of a cysteine protease cascade and subsequent cleavage
of various cellular components, resulting in apoptotic cell
death. Cells undergoing apoptosis are characterized by specific
morphological changes, including cellular shrinkage, multiple
buds and protrusions, and nuclear chromatin condensation
ultimately leading to DNA fragmentation. Another and less well
known form of cell death is "oncosis". A number of noxious
stimuli and ischemia are known to lead to cell death with
morphological changes distinct from apoptosis. The term
"necrosis" is often used to describe cell death lacking the
characteristics of apoptosis. However, the term "necrosis" does
not describe a specific pathway of cell death, but instead refers
to the intracellular degradative reactions occurring after the
death of individual cells within a living organism by any
mechanism, including apoptosis. The term "oncosis", which derives
from "onkos" ("swelling"), was first used in 1910 to describe
ischemic cell death in osteocytes, and the term was reintroduced
recently to describe a form of cell death distinct from
apoptosis. Oncotic cells are characterized by cell swelling,
organelle swelling, vacuolization, and increased membrane
permeability. Oncosis usually occurs rapidly after application of
the injury, with early changes resulting in alterations in cell
shape and volume. In monolayer cell culture, oncotic cells form
cytoplasmic blebs and chromatin clumps, followed by cells pulling
apart, rounding up, and detaching from the substrate. Oncotic
cell death has been documented in various circumstances,
including virulent infection by certain pathogens.
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Proc. Nat. Acad. Sci. 2001 98:9778
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12. ON AMYLOID FIBRILS
J. Zurdo et al (Oxford Center for Molecular Sciences, UK) discuss
amyloid fibrils. Amyloid fibrils are highly proteinaceous
aggregates associated with pathogenic conditions such as
Alzheimer's disease and the spongiform encephalopathies. Such
fibrils are also being explored as novel nanostructures with a
wide variety of potential applications. Despite the considerable
advances in the characterization of these fibrils, there are
still a number of important aspects of their structure that
remain unclarified. Among these aspects are the detailed
definition of the conformational state of the protein chains
within an amyloid fibril and the manner in which the constituent
protofilaments are assembled. Investigations of such questions
are currently hindered by the intrinsic heterogeneity of fibril
samples prepared in vitro, as these invariably contain soluble
precursors and nonfibrillar aggregates. The development of
strategies to isolate fibrils is therefore of great importance.
The authors report a method to achieve this objective: amyloid
fibrils free of amorphous aggregates and soluble precursors can
be prepared by using a combination of proteolytic digestion and
ultra-centrifugation. The authors report this approach has
enabled them to demonstrate that the full-length protein is
preserved within the fibrils they studied, and spectroscopic
analysis indicates that the proteins within the fibrils have a
beta-sheet structure mainly parallel in character. Other regions
of the polypeptide chain appear to form turns and disordered
structures that are likely to link the beta-strands. The authors
suggest their approach should be applicable to a wide range of
amyloid systems, and should be important not only in
investigating disease-related aggregates but also in the
preparation and characterization of novel materials assembled
from protein fibrils.
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J. Am. Chem. Soc. 2001 123:8143
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SCIENCE-WEEK 21 Dec 2001 http://scienceweek.com
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13. POSTDOCTORAL FELLOWSHIP PROFILES:
Laboratory of Tallie Z. Baram
-----------------------------
Installation: University of California at Irvine (US)
Department: Anatomy/Neurobiology (and Pediatrics)
General research area: Neuroscience
Head of this specific laboratory: Tallie Z. Baram, MD PhD
http://www.ucihs.uci.edu/anatomy/baram.html
Postdoctoral fellowships are available in the following
specific research problems:
1) Use of gene chip array and related methods to study the
mechanisms of epileptogenesis induced by experimental febrile
seizures. See: Toth et al, "Seizure-induced neuronal injury:
vulnerability to febrile seizures in an immature rat model". J.
Neurosci. 18:4285-4294 (1998); Baram TZ and Hatalski CG,
"Neuropeptide-mediated excitability: A key triggering mechanism
for seizure generation in the developing brain?. Trends Neurosci.
21:471-476 (1998). Chen et al, "Febrile seizures in the immature
brain result in persistent modification of neuronal excitability
in limbic circuits". Nature Medicine 5:888-894 (1999). Dube et
al, "Prolonged febrile seizures in the immature rat model enhance
hippocampal excitability long-term". Ann. Neurol. 47:336344
(2000). Book: _Febrile Seizures_. Baram TZ and Shinnar, S.
Editors. Academic Press, 2001.
2) Use of Organotypic hippocampal slice culture to study the
regulation of expression of hyperpolarization activated cyclic
AMP modulated channels (HCNs). See: Bender et al, "Differential
and age-dependent expression of hyperpolarization-activated
cyclic Nucleotide-gated cation channel isoforms 1-4 suggest
evolving roles in the developing rat hippocampus". Neuroscience,
106: 689-698 (2001). Bender et al, "Enhanced CREB phosphorylation
in immature dentate gyrus granule cells indicates a specific role
for CREB in granule cell differentiation". European J. Neurosci.
13:679686 (2001). Brewster et al, "Transcriptional control of
neuronal pacemakers: activity regulated expression of the
hyperpolarization-activated cyclic nucleotide-gated channel
molecules". (AES abstract, 2001)
Previous research experience and degrees required:
For 1st position: Extensive molecular biology training
required; experience with chip array highly desirable. Training
in neuroscience highly desirable.
For 2nd position: Experience with hippocampal structure
and function required. Experience with in vitro methods highly
desirable.
Usual starting stipend: To be determined, based on the
candidate's qualifications.
Special requirements concerning citizenship, visas, etc.:
These positions are funded by NIH grants. Truly outstanding
candidates will be considered regardless of visa status.
Approximate number of people currently working in this
specific laboratory (faculty, staff, students, postdocs): 10
More information: Michele Hinojosa. Email: mhinojos@uci.edu
Further relevant information: Kindly apply only if you are
qualified and are truly interested in the projects.
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14. IN FOCUS: ON WEATHER IN THE TROPICS
"In tropical lands, the seasons are difficult to differentiate
because of the slight temperature variation between them -- if
one exists at all. Even so, the terms 'summer' and 'winter' are
commonly used in Venezuela and other tropical countries, but
their meanings in those countries have more to do with rainfall
than with temperature. Rainy periods are called winter; sunny
one, summer. A European or North American visitor who experiences
the two seasons in the same day may not think of them as seasons.
The ratio between annual and diurnal variation defines one of the
major definitions of tropical and temperate climates: The diurnal
is of greater amplitude than the annual in temperature near the
equator, and particularly in desert regions, where the daily
temperature range is greatest. Venezuela is among the tropical
countries that such violent weather as tornadoes and hurricanes
rarely touches. Wind speeds of more than about 40 miles (65
kilometers) per hour are rare; indeed, the flimsy roof
construction, which would never withstand a major storm, verifies
this. Some coastal areas in the Tropics do suffer the onslaughts
of hurricanes and typhoons. The coast of Bangladesh, facing the
Bay of Bengal, consists of many low-lying islands hardly above
sea level, and consequently of no protection against storms. The
sea swell alone can take many lives, and many of the major
disasters of the 20th century involving loss of life occurred on
the Bangladesh coastal plains. Of the nine natural disasters in
the last century that have each taken more than 100,000 lives,
two resulted from tropical storms striking Bangladesh; three from
floods in China; and four from earthquakes, three in China and
one in Japan. The six most lethal storms took place in the Bay of
Bengal.
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A. Upgren and J. Stock: _Weather: How it Works and Why it
Matters_
(Perseus Publishing, Cambridge MA 2000, p.167)
http://www.amazon.com/exec/obidos/ASIN/0738205214/scienceweek
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SCIENCE-WEEK 21 Dec 2001 http://scienceweek.com
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15. FROM PRAXIS:
ON THE INFLUENZA PANDEMIC OF 1918
Robert G. Webster (St. Jude Children's Research Hospital Memphis,
US) discusses the 1918 influenza epidemic. Two influenza
outbreaks in the 20th century challenge current beliefs about
patterns of influenza virulence. The "Spanish flu" pandemic of
1918, rather than sparing young healthy adults, killed millions
in the prime of life. The pandemic wiped out entire villages at
opposite ends of the Earth and depressed world population growth
for 10 years. In 1997, a lethal avian influenza virus was
transmitted directly to humans from chickens in Hong Kong: 6 of
18 clinically diagnosed human cases were fatal, and again, many
of the victims were young adults. Both of these outbreaks suggest
the emergence of highly virulent influenza variants.
Unfortunately, until the basis of influenza virulence is
understood, the human population will be defenseless against
similar outbreaks in the future. The virulence of a virus is
defined by its comparative capacity to produce disease in a host.
The 1918 Spanish flu virus was extremely virulent: it killed 10
times as many persons in the US as did the 1957 Asian flu and
approximately 20 times as many people as the 1968 Hong Kong flu.
The human population is most vulnerable to influenza viruses that
have new antigenic properties. It now takes approximately 6
months to prepare an appropriate vaccine. Although advances in
reverse genetics will shorten this time, several months will
still be needed to prepare a vaccine, and during the period
between the detection of a pandemic strain and the availability
of a vaccine, antiviral drugs will be essential. It is gravely
disquieting that no action has yet been taken to create strategic
stockpiles of such antiviral drugs.
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Science 2001 293:1773
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PRAXIS 17 Dec 2001 http://scienceweek.com/praxis
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Related Background:
THREAT OF EMERGING VIRUSES
One result of globalization is the increasing ease with
which exotic and dangerous pathogens, particularly viruses, can
cross borders. A number of extremely virulent viruses have
recently been the focus of attention of various government public
health agencies in the US and Europe, and some researchers
believe major outbreaks may be unavoidable in the near future.
Arenaviruses include several causative agents of fatal human
hemorrhagic fevers. These are spherical viruses, 50-300
nanometers in diameter. The genome is 10-14 kilobases in size and
consists of 2 single-stranded RNA molecules. Some of these
viruses establish chronic infections in rodents, and humans are
infected by contact with rodent excreta. "Hemorrhagic fevers" is
a generic term for a number of different diseases caused by
different viruses (one type of which are the arenaviruses).
Common elements are high fever, organ bleeding, hypotension,
shock, etc. Included in this group of diseases are Lassa fever,
Ebola fever, Marburg virus fever, Machupo virus, etc., all of
which are considered emerging viruses of potential danger to
developed countries.
Marburg virus is one of the two notorious African
hemorrhagic fevers (the other is Ebola virus). Marburg virus is
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.
Ebola virus, together with Marburg virus, makes up the
"filovirus" family. This now notorious group of viruses was
discovered in 1967 when Marburg virus was identified as the
etiologic agent of a hemorrhagic fever outbreak in research
facilities in Europe that handled tissues from African green
monkeys imported from Uganda.Subsequently, Ebola viruses were
shown to be the cause of simultaneously occurring hemorrhagic
fever outbreaks in 1976 in the Democratic Republic of Congo
(formerly Zaire) and Sudan. These outbreaks were shown to be
caused by two different subtypes of Ebola virus, which became
known as the Zaire and Sudan subtypes. Mortality rates of up to
80 percent occurred in these and more recent outbreaks in
1995-1996. Despite considerable efforts to identify the natural
reservoir for Ebola and Marburg viruses, the host species remains
unknown.
The first recognized cases of Lassa fever occurred in 1969
among Americans stationed in the Nigerian village of Lassa. This
virus is also extremely virulent, with a mortality rate ranging
from 36 to 67 percent. Lassa virus is active in all western
African countries between Senegal and Zaire, and in Sierra Leone
Lassa fever accounts for 10 percent of all fever patients
admitted to hospitals and for almost 2 percent of the general
mortality rate. Lassa fever can involve almost all the organ
systems, with the disease characterized by very high fever, mouth
ulcers, severe muscle aches, skin rash with hemorrhages,
pneumonia, and heart and kidney damage. A species of house rat is
the primary rodent reservoir of the virus, but the virus can be
transmitted by human-to-human contact.
Machupo virus, also called Machupo hemorrhagic fever, is
another name for Bolivian hemorrhagic fever. This viral disease
was first identified in Bolivia in 1962, when it was estimated
that 2000 to 3000 persons were infected with the disease, with a
fatality rate of 20 percent. Sporadic outbreaks continue to occur
in Bolivia.
In a medical context, an "inflammation" is a complex
pathological process occurring in a tissue in response to injury
or invasion by various agents. In general, the term
"encephalitis" refers to any inflammatory disease of the brain,
and "viral encephalitis" is such a disease caused by direct viral
invasion.
The term "arbovirus" is a general designation for any
ARthropod-BOrne virus, with more than 250 genomically distinct
arbovirus entities ("species") currently recognized, of which at
least 80 distinct arboviruses cause diseases in humans.
Arboviruses are transmitted among vertebrates by biting insects,
primarily mosquitoes and ticks. Birds are often the sources of
infection for mosquitoes, which then transmit the infection to
domestic animals and humans. Flaviviruses are a family of 70
genomically different arboviruses 45 to 60 nanometers in
diameter, the viruses with a single-stranded RNA genome and a
viral envelope containing lipid and two glycoproteins.
Flaviviruses are usually transmitted between vertebrates by
mosquitoes and ticks, and many of these viruses have worldwide
distribution.
West Nile Fever is an acute febrile disease that occurs in
the Middle East, tropical and subtropical Africa, and southeast
Asia. The disease is usually mild, but sometimes it is fatal, and
it is caused by a flavivirus.
In late August and early September 1999, New York City and
surrounding areas experienced an outbreak of human encephalitis
consistent with an arboviral etiology. Two independent research
groups have now provided evidence that the viral pathogen in this
outbreak was West Nile virus probably transmitted from birds to
humans via mosquitoes.
In 1999, R.S. Lanciotti and colleagues pointed out that the
New York encephalitis outbreak was concurrent with extensive
mortality in crows as well as the deaths of several exotic birds
at a zoological park in the same area. Complete genome sequencing
by the authors of a flavivirus isolated from the brain of a dead
Chilean flamingo, together with partial sequence analysis of
viral envelope glycoprotein genes amplified from several other
species (including mosquitoes and two fatal human cases),
revealed the West Nile virus was responsible for the 1999 human
disease outbreak in New York City. This research team also
pointed out that the northeastern US outbreak was the first
documented incidence of the West Nile virus in the Western
Hemisphere. The recent epidemic of West Nile virus in New York
City is unprecedented and underscores the ease with which
pathogens can move among the population centers of the world. It
is not yet known how the virus was introduced, nor how long it
has been in the US. The extent of its geographic distribution
remains a mystery, as does the long-term impact it may have on
human and animal health. The researchers suggested the West Nile
virus could have entered the Western Hemisphere through a number
of mechanisms, including travel by infected humans, importation
of illegal birds or other domestic pets, or unintentional
introduction of virus-infected ticks or mosquitoes.
Dengue is a human disease caused by a virus, which in turn
is transmitted by a mosquito (Aedes aegypti) through a mosquito
bite. In some place, the disease may be called "breakbone fever"
or "dandy Fever". The disease is endemic throughout the tropics
and subtropics, and in adults an attack of dengue fever usually
lasts several weeks and then it passes. There is a variant,
however, that infects children, dengue hemorrhagic fever, and
this has a mortality rate of as much as 30%, most deaths
occurring in infants less than a year old. Dengue hemorrhagic
fever is prevalent in Southeast Asia, China, and Cuba. An
important fact about the disease vector, the mosquito Aedes
aegypti, is that it likes to breed around human dwellings and in
man-made containers. Which leads to the expectation that dengue
could be eradicated by a concerted effort to eliminate containers
and other man-made debris used by the breeding mosquito. Such
concerted efforts have been underway now for 50 years, and
apparently they have all failed and the mosquito Aedes aegypti
has been victorious. In July 1997, there was a report of a
serious outbreak of dengue in Santiago, Cuba, with estimates of
the number of cases as high as 30,000.
A recent report indicates that interest in the risks posed
by highly contagious fatal pathogens is prompting several US
universities to set up special laboratories and research programs
to study emerging microorganisms. Some of the deadly microbes
targeted for study include Ebola, Marburg, and Lassa fever
viruses from Africa. There is also interest in other arenaviruses
previously found in Latin America but now identified in
California. West Nile virus and dengue fever virus are also
emerging as potential threats to public health, and there is
apparently growing official concern about possible bioterrorism
involving agents such as anthrax and Bolivia's machupo virus. The
report states that some researchers are complaining about a lack
of academic facilities, since by regulation such research must be
housed in laboratories with a safety designation known as
Biosafety Level 4. It is hoped that government funds will become
available to build new facilities.
-----------
Science 1999 286:2333
Nature 2001 411:727
PRAXIS 2001 6 Aug
-------------------
Related Background:
MEDICAL BIOLOGY: EMERGING VIRAL DISEASES
An argument can be made that after the genome of the living
cell, the most important cellular entity is the ribosome, or more
exactly the ribosomes of the cell, since although each cell
contains only one genome, each cell contains many thousands of
ribosomes. The reason for the importance of ribosomes is simple:
the genome contains programs for the ultimate synthesis of
proteins, the molecules that do the work of the cell, but these
programs are translated into chemical action in the ribosomes --
it is the ribosomes that do the actual synthesis of proteins.
Genetic information flow in a biological cell can be
described as "transcription" to "translation". In general,
transcription is the process whereby genome DNA code is
transcribed into RNA code, ultimately in the form of "messenger
RNA" (mRNA), and messenger RNA in turn is essentially a tape that
feeds into ribosomes one triplet nucleotide base unit (codon) at
a time to program the sequence of amino acids of a polypeptide,
the protein synthesis process called "translation": the messenger
RNA polymer tape goes into the ribosome codon by codon, and the
synthesized protein polymer product comes out of the ribosome
amino acid by amino acid.
In the context of viruses, what is important is that viruses
do not contain the protein catalysts (enzymes) required for their
own replication, and they must therefore parasitize host cells
and by one of various means get the ribosomes of such host cells
to manufacture viral proteins, including the enzymes necessary to
catalyze the replication of the viral genome. The final complete
virus (virion) is thus assembled from components provided by the
host cell, the virus essentially programming the synthesis of its
own parts.
Concerning the genomes of viruses, there are two general
types, the DNA viral genome and the RNA viral genome. Only in
certain viruses do we find genomes consisting of RNA; all
biological cells (and they are all potential hosts for viruses)
contain DNA genomes. There are more than 2500 groups of different
viruses now recognized and at least partially characterized, and
a variety of logical classifications of viruses exist, but
certainly one useful broad classification scheme differentiates
viruses into various DNA viruses and various RNA viruses, with
each type of virus having a more or less different challenge once
it enters a host cell. But in each case, for both DNA and RNA
viruses, the general challenge is the same: directly or
indirectly the viral genome must bring about the production of
the messenger RNAs necessary to get the host ribosomes to produce
the proteins necessary for viral replication.
In general, with some types of RNA viruses, the RNA genome
("plus-sense"; "positive-strand") can itself act as messenger RNA
for host ribosomes; while other types of RNA viruses, the RNA
genome ("minus-sense"; negative-strand) must first produce a
complementary RNA, which then acts as messenger RNA for the host
ribosomes. The replication process in minus-sense RNA viruses is
complex, since host cells do not carry enzymes that can
polymerize complementary RNA from an RNA template, and such
viruses therefore must carry their own special enzymes ("RNA-
dependent transcriptases") to achieve this synthesis.
In this context, the term "segmented genome" refers to a
genome that consists of more than one nucleic acid molecule.
Depending on the type of virus, some viral genomes are segmented,
while others are unsegmented.
... ... S.T. Nichol et al (3 authors at 3 installations, US JP)
present a short review of some emerging diseases caused by RNA
viruses, the authors making the following points:
1) The authors point out that RNA viruses can quickly adapt
to and exploit varying environmental conditions because of the
high error rates of the virus enzymes (polymerases) that
replicate their genomes. It is not surprising, therefore, that
several recent prominent examples of emerging or re-emerging
diseases are caused by RNA viruses. However, a complex interplay
of factors can influence disease emergence. In addition to virus
genetic variation (mutation, *recombination, and *reassortment),
environmental factors (including ecological, social, health care,
and behavioral influences) can play important roles.
2) Influenza virus strains that cause worldwide outbreaks
(pandemics) are classic examples of emerging viruses that are
maintained in non-human animal hosts before transmission to
humans. Influenza viruses are isolated from a variety of animals,
including humans, pigs, horses, wild and domestic birds, and even
sea mammals. The most devastating viral infection of the past 100
years was not that caused by human immunodeficiency virus (HIV),
but by Spanish influenza (1918-1919), which killed more than 20
million people worldwide. Genetic studies suggest that the
Spanish influenza virus originally was derived from birds.
Furthermore, the causative virus for the 1957 and 1968 influenza
pandemics were hybrids between human and avian influenza viruses.
Because humans did not have immunity to avian influenza viruses,
the hybrid viruses produced devastating consequences: 70,000 and
46,500 deaths worldwide in the 1957 and 1958 pandemics,
respectively.
3) Hantaviruses are segmented RNA viruses belonging to the
genus Hantavirus in the family Bunyaviridae (*Note #1).
Hantaviruses are maintained in various rodent reservoirs in which
the hosts are persistently infected without disease symptoms.
Specific hantaviruses transmitted from the contaminated urine and
feces of infected rodents cause two important human diseases,
*hemorrhagic fever with renal syndrome and hantavirus pulmonary
syndrome. Annually, hundreds of thousands of cases of the former
are reported throughout Euro-Asia, whereas hundreds of cases of
the latter are reported in North and South America. Because
rodents act as the natural reservoirs for hantaviruses and human-
to-human infections are rare, understanding the ecology of
hantaviruses within their natural reservoir is important for
preventing and controlling the emergence of such diseases. The
comparison of many hantavirus genomes from different rodent
species has shown a clear correlation between the rodent species
and the virus genotype, suggesting that hantaviruses have co-
evolved with their natural hosts for more than 20 million years,
since before the first humans evolved.
4) Ebola virus is a nonsegmented RNA virus, which together
with Marburg virus makes up the "filovirus" family. This now
notorious group of viruses was discovered in 1967 when Marburg
virus was identified as the etiologic agent of a hemorrhagic
fever outbreak in research facilities in Europe that handled
tissues from African green monkeys imported from Uganda.
Subsequently, Ebola viruses were shown to be the cause of
simultaneously occurring hemorrhagic fever outbreaks in 1976 in
the Democratic Republic of Congo (formerly Zaire) and Sudan.
These outbreaks were shown to be caused by two different subtypes
of Ebola virus, which became known as the Zaire and Sudan
subtypes. Mortality rates of up to 80 percent occurred in these
and more recent outbreaks in 1995-1996. Despite considerable
efforts to identify the natural reservoir for Ebola and Marburg
viruses, the host species remains unknown.
5) Nipah virus is a newly discovered member of the
paramyxovirus family of nonsegmented RNA viruses. This virus was
responsible for a viral encephalitis outbreak in Malaysia that
was first recognized in October 1998 and ended in midsummer 1999.
This outbreak resulted in almost 300 confirmed infections, with a
mortality rate for hospitalized infections of approximately 35
percent. Fruit bats of the genus Pteropus have been implicated as
the likely virus reservoir. The virus was apparently first
introduced into pigs, where close contact caused by intensive
farming practices led to efficient pig-to-pig transmission, and
subsequently pig-to-human transmission. Virtually all human cases
were in close proximity to the infected pigs.
6) The authors conclude: "These examples highlight the
subtle balance of environmental and genetic factors that can mold
the diverse evolutionary patterns observed for RNA viruses and
illustrate the complexity of these systems, which makes it
difficult to predict future viral disease emergences."
-----------
Proc. Nat. Acad. Sci. 2000 97:12411
-----------
Notes:
... ... *recombination: In this context, in general, the term
"recombination" refers to the mixing of genes from two or more
types, strains, etc: i.e., a process that produces a mixed genome
that differs from the original genome by containing parts of the
genome(s) of one or more other types of viruses.
... ... *reassortment: In this context, in general, the term
"reassortment" refers to the mixing of genome and protein coat in
a virus: i.e., a process that produces a virus of one type that
contains the protein coat of a virus of another type. Since the
immune system is usually responding to the protein coat of a
virus, a reassortment, for example, that provides a formerly
docile virus with a protein coat not initially recognized by the
immune system can make that virus suddenly extremely dangerous.
... ... *Note #1: Although many authors insist on labeling
viruses with the standard nomenclature used for animals and
plants, it can be argued that since it is not clear that viruses
have a common origin, a classification scheme involving family,
genus, species, etc. (Linnaean classification) is not justified.
... ... *hemorrhagic fever: The hemorrhagic fevers, of which
there are a number of types, are marked by a cluster of severely
debilitating symptoms, and especially by capillary bleeding
(hemorrhaging).
-----------
ScienceWeek 2000 15 Dec
-----------
PRAXIS 17 Dec 2001 http://scienceweek.com/praxis
-----------
SCIENCE-WEEK 21 Dec 2001 http://scienceweek.com
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
16. This week in PRAXIS (17 Dec 01):
-------------------------------
1. Biodiversity and Agri-Environment Schemes: Evidence for Lack
of Protection
2. p53 Protein as a Target in Cancer Therapy
3. On Dyslexia
4. Saving Biodiversity
5. Influenza Pandemic of 1918
6. Analysis of Genomic Data
7. On Ecosystem Functioning
8. Identifying Targets for Antibiotic Discovery
9. Zeolites and Fluoride Ions
10. Quantum Engineering and Pointer States
11. Adsorbents and the Adsorption Process
12. Electronic Wavefunctions in Carbon Nanotubes
For information about PRAXIS, see:
http://www.scienceweek.com/praxis
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