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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.
May 18, 2001 -- Vol. 5 Number 20
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There ain't no rules around here! We're trying
to accomplish something!
-- Thomas Edison (1847-1931)
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Section 1
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Contents of this Issue (Full reports in Section 2):
1. EPIDEMIOLOGY: BACTERIAL POPULATION GENETICS AND DISEASE
Evolutionary theory suggests that microbes evolve to a level of
virulence that maximizes their transmission from one host to
another. This requires that microbes balance the benefit of
achieving high numbers with the risk of killing or incapacitating
the host and thereby reducing the length of time available for
transmission. Although useful in analysis of some pathogens, this
explanation is hard to reconcile with the life-styles of those
infectious agents, particularly commensal bacteria, that appear
to thrive by colonizing their hosts without producing host
disease symptoms, and yet cause severe disease when they breach
the normal barriers of the host and enter the bloodstream.
Commensal bacteria include a diverse range of microbes that are
carried in the gastrointestinal tract, nose, or throat, or on the
skin of their human hosts. These organisms colonize their hosts
without causing symptoms, with symptom-producing infection a
rare, often accidental, and probably "dead-end" event.
(Marc Lipsitch: Science 6 Apr 01 292:59)
2. MEDICAL BIOLOGY: ON NEURODEGENERATIVE DISEASES AND PRIONS
Nearly all neurodegenerative disorders involve abnormal
processing of neuronal proteins. The aberrant mechanism can
involve a misfolding of proteins, altered *post-translational
modification of newly synthesized proteins, abnormal proteolytic
cleavage, anomalous gene splicing, improper gene expression, or
diminished clearance of degraded protein. Misprocessed proteins
often accumulate because the cellular mechanisms for removing
them are ineffective, and the particular protein that is
improperly processed determines the malfunction of distinct sets
of neurons and thus the clinical manifestation of the disease.
Prions are infectious proteins that in mammals replicate by
recruiting normal cellular prion protein and stimulating its
conversion to the disease-causing prion isoform. A major feature
that distinguishes prions from viruses is that abnormal prion can
be encoded by a chromosomal gene resulting from a mutation of the
normal prion gene.
(Stanley B. Prusiner: New England J. Med. 17 May 01 344:1516)
3. PHYSIOLOGY:
ON THE ACCURACY OF SOUND LOCALIZATION IN AN INSECT
Humans use at least two different strategies to localize the
horizontal position of sound sources, depending on the
frequencies in the stimulus. For frequencies below 3000 hertz,
interaural time differences are used to localize the source;
above these frequencies, interaural intensity differences are
used as cues. The longest interaural time differences in humans,
which are produced by sounds arising directly lateral to one ear,
are on the order of only 700 microseconds (the width of the head
divided by the speed of sound in air). Experiments, however,
demonstrate that humans can actually detect interaural time
differences as small as 10 microseconds, and this sensitivity
translates into an accuracy for sound localization of
approximately 1 degree. New experiments demonstrate that the
parasitoid fly O. ochracea can behaviorally localize a sound
source with a precision equal to that of humans.
(A.C. Mason et al: Nature 5 Apr 01 410:686)
4. THEORETICAL PHYSICS:
ON THE EQUILIBRIUM MECHANICAL PROPERTIES OF INDIVIDUAL MOLECULES
Recent advances in the micromanipulation of single molecules have
led to new insights into the dynamics, interactions, structure,
and mechanical properties of individual molecules. Single-
molecule manipulation with an atomic force microscope, laser-
tweezer stretching, and analogous computer experiments have
revealed details about unfolding and unbinding events of
individual proteins and their complexes. In an atomic-force-
microscope experiment, a single molecule is subjected to a time-
varying external force, e.g., by pulling on the end of a linear
polymer. The applied force is determined from the time-dependent
position of the cantilever tip with respect to the sample.
A quantitative theoretical analysis demonstrates how equilibrium
free energy profiles can be extracted rigorously from repeated
non-equilibrium force measurements on the basis of an extension
of Jarzynski's identity between free energies and irreversible
work. (G. Hummer and A. Szabo: PNAS US 27 Mar 01 98:3658)
5. PLANETARY SCIENCE: ON THE MOON GANYMEDE
With a diameter of 5262 kilometers, Ganymede is not only the
largest moon of Jupiter, but also the largest moon in the Solar
System -- in fact, Ganymede is larger than the planet Mercury.
Ganymede orbits Jupiter at a distance of approximately 1 million
kilometers, and it has a relatively low density of 1.93 grams per
cubic centimeter, which suggests a composition approximately half
rock and half ice by mass. Researchers now report digital
elevation models of parts of the surface of Ganymede, the models
derived from stereo pairs combining data from the Voyager and
Galileo spacecraft, which reveal bright and smooth terrains that
lie at roughly constant elevations 100 to 1000 meters below the
surrounding rougher terrains. These topographic data, together
with new images that show fine-scale embayment and burial of
older features, indicate that the smooth terrains were formed by
flooding of shallow structural troughs by low-viscosity water-ice
lavas. (P.M. Schenk et al: Nature 1 Mar 01 410:57)
6. HISTORY OF SCIENCE: ON LANGUAGE REFORM IN CHEMISTRY
An argument can be made that nomenclature in science is as
important as data, since nomenclature represents the prevailing
conceptual organization of observations. The language reform of
1787-1789 was an integral part of the formation of the autonomous
discipline of chemistry, contributed to the subordination of
pharmacy to chemistry, and contributed to the redefinition of the
chemical arts as applied chemistry. The new language forged by
academic chemists separated many users of chemical substances
from their own traditions. The new language ignored the
physiological senses of chemists, banished all reference to
geographical origins or the discovery of the substances, and
imposed an analytical quantitative logic on chemical
nomenclature. Although the use of this logic proved to be a
valuable method over time, the principles of the system were
never strictly applied.
(Bernadette Bensaude-Vincent: Nature 22 Mar 01 410:415)
7. IN FOCUS: ON PLANCK, BOLTZMANN, AND ENTROPY
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Section 2
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1. EPIDEMIOLOGY: BACTERIAL POPULATION GENETICS AND DISEASE
Bacteria are classified as "prokaryotes", and the primary
distinguishing characteristics of prokaryotes are their
relatively small size, on the order of 1 micron in diameter, and
the absence of a nuclear membrane. The DNA of almost all bacteria
consists of a circular molecule with a length of approximately 1
millimeter, this comprising the so-called prokaryote
"chromosome". The specialized region of a bacterium that contains
the DNA is called the "nucleoid, and it can be observed with
electron microscopy. Thus, it is not true that subcellular
differentiation, clearly demarcated by membranes in eukaryotes,
is lacking in prokaryotes. Indeed, some prokaryotes form
membrane-bound subcellular structures with specialized function,
e.g., chromophores of photosynthetic bacteria. However, such
prokaryotic structures differ from eukaryotic counterparts in
that the membranes in prokaryotes that surround specialized
regions are extensions of the cell membrane and not separate
membrane entities.
Another distinguishing characteristic of prokaryotes is
their ability to exchange small packets of genetic information.
In many cases, this genetic information is carried on "plasmids",
small and specialized genetic elements that are capable of
replication within at least one prokaryotic cell line. In some
cases, plasmids may be transferred from one cell to another, thus
carrying sets of specialized genetic information through a
bacterial population. Some plasmids have a broad host range that
allows them to convey sets of genes to diverse organisms. Of
particular concern are drug-resistance plasmids that may render
diverse bacteria resistant to antibiotics.
The single circle comprising the bacterial chromosome
contains approximately 4 million base pairs of DNA. Plasmid base
pairs range in number from a few thousand to 100,000. The DNA
genome entities (chromosome and plasmid) that contain genetic
information necessary for their own replication are called
"replicons".
Many bacterial species exhibit a type of association with
large eukaryote species called "commensalism". In such an
association the "commensal" (the bacterium) gains some benefit
(e.g., surplus food), while the other party (the host) suffers no
serious disadvantage. In "mutualism", members of two different
species benefit and neither suffers disadvantage. In
"parasitism", one party gains considerably at the other party's
expense. Certain species of bacteria resident in the human
gastrointestinal tract are examples of mutualism. Other bacterial
species, in the gastrointestinal tract and elsewhere (e.g., in
the nostrils) are examples of commensalism. Many disease states
involve an altered virulence of bacteria once translocated from
the part of the body they normally occupy to some other part. For
example, ordinarily harmless human gastrointestinal bacteria
(e.g., Escherichia coli) transferred from the gastrointestinal
tract to an open wound and/or the blood system can cause serious
infection. In other cases, bacteria that are ordinarily involved
in commensalism or mutualism may undergo mutation into a virulent
strain.
In general, the term "population genetics" refers to the
study of the genetic composition of populations, with one
approach the estimation of gene frequencies and detection of the
selective influences that determine these gene frequencies in
natural populations. A good deal of the work in this field
involves the construction of mathematical models of the influence
of various factors (e.g., selection, population size, mutation)
upon the fixation and loss of linked and unlinked genes.
... ... Marc Lipsitch (Harvard University, US) presents a
commentary on current research in bacterial population genetics
and disease, the author making the following points:
1) The author poses the question: What makes a successful
pathogen? Genetic studies have addressed this question by
focusing on the mechanisms by which pathogens cause disease
(pathogenesis), i.e., how pathogens infect hosts, evade the host
immune system, secrete toxins, and interrupt and co-opt host
signaling pathways. Evolutionary theory suggests that microbes
evolve to a level of virulence that maximizes their transmission
from one host to another. This requires that microbes balance the
benefit of achieving high numbers with the risk of killing or
incapacitating the host and thereby reducing the length of time
available for transmission.
2) The author suggests that although useful in analysis of
some pathogens, this explanation is hard to reconcile with the
life-styles of those infectious agents, particularly commensal
bacteria, that appear to thrive by colonizing their hosts without
producing host disease symptoms, and yet cause severe disease
when they breach the normal barriers of the host and enter the
bloodstream. Commensal bacteria include a diverse range of
microbes that are carried in the gastrointestinal tract, nose, or
throat, or on the skin of their human hosts. These organisms
colonize their hosts without causing symptoms, with symptom-
producing infection a rare, often accidental, and probably "dead-
end" event. How do the genetically and biochemically complex
factors that produce virulence contribute to the evolutionary
success of commensal bacteria?
3) The author suggests that epidemiologists and other
researchers who study how microbes cause disease have been
skeptical about the relevance of evolutionary biology and
population genetics to their disciplines. However, this is
beginning to change as researchers recognize the importance of
pathogen population structure for understanding antimicrobial
resistance, interactions between pathogens and the immune system,
identifying candidate antigens for vaccines, and predicting and
assessing the effectiveness of vaccination programs. Recent work
demonstrates that studies of the population genetics of an
infectious agent can generate hypotheses about microbial
pathogenesis that are both new and experimentally testable.
Recent work also demonstrates that a complete understanding of
the epidemiology and transmission of infectious disease depends
on a clear picture of the population genetics of the causative
organism.
-----------
Marc Lipsitch: Bacterial population genetics and disease.
(Science 6 Apr 01 292:59)
QY: Marc Lipsitch: mlipsitc@hsph.harvard.edu
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Summary by SCIENCE-WEEK http://scienceweek.com 18May01
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
IMPLICATIONS OF ANTIBIOTIC RESISTANCE IN WILD RODENTS
During this century, the use of antibiotics profoundly changed
the face of clinical medicine and saved many thousands of lives
worldwide. A variety of infections that were considered dangerous
during the early decades of the century, when antibiotics were
unknown, are now routinely and successfully treated by various
antibiotics or "antimicrobial" agents [*Note #1]. In general, the
term "antibiotic" refers to a chemical substance, produced by one
kind of microorganism, which has the capacity in low
concentrations to inhibit the growth of or to destroy
microorganisms of another kind. The first antibiotic to receive
widespread attention was penicillin, which was developed to meet
the need for an effective anti-infectious agent during World War
II. Penicillin and certain other classes of antibiotics are
secreted by strains of various molds, but in recent decades
pharmaceutical chemical synthesis has produced a wide variety of
substances with antibiotic action, and the availability of
antibiotics is no longer completely dependent on natural sources.
That progress, however, has been tempered by the appearance of a
potentially serious problem -- the evolution, presumably by
conventional evolutionary selection pressures, of pathological
bacterial strains resistant to antibiotics currently in use. For
some time, the consensus view concerning microbial resistance to
antibiotics has been that the clinical overuse of antibiotics is
the cause of the problem, and that a reduction in antibiotic
usage will reduce or even reverse such resistance. Unfortunately,
as the present report and other reports indicate, the problem may
be more intractable than expected. ... ... M.A. Gilliver et al
(University of Liverpool, UK) now report that antibiotic
resistance is prevalent in populations of wild rodents that have
not been exposed to antibiotics, indicating that approaches to
control of resistance based on the over-use assumption may be
overly optimistic. The study reported by the authors involved a
survey of *commensal enteric Enterobacteriaceae isolated from two
wild populations of small rodents (bank voles and wood mice). The
antibiotics whose effectiveness was examined were tetracycline,
trimethoprim, naladixic acid, chloramphenicol,
amoxycillin/clavulanic acid, amoxycillin, and cefuroxime. The
authors suggest their results indicate that resistance to
antibiotics is widespread in at least some wild populations, even
though these populations have never to their knowledge been
exposed to antibiotics, and that these results undermine the
presumption that resistance will decline in the absence of
antibiotic treatment. The authors suggest that the origin of the
resistance and the selection mechanisms ("if indeed such
mechanisms are necessary") responsible for maintaining a high
prevalence of resistance are unknown. Finally, the authors
suggest that "it is important to address these questions, not
least because similar mechanisms may operate in farm animals and
humans, in which case the management of antibiotic resistance may
need to be reconsidered."
-----------
M.A. Gilliver et al: Antibiotic resistance found in wild rodents.
(Nature 16 Sep 99 401:233)
QY: C. Anthony Hart: c.a.hart@liverpool.ac.uk
-----------
Text Notes:
... ... *Note #1: In general, biologists recognize a variety of
categories of "microbes" (microorganisms): e.g., yeasts, molds
(fungi), streptomycetes, protozoa, bacteria, rickettsiae,
viruses, etc. A large proportion of the infectious diseases of
animals and humans is caused by 3 of these groups: bacteria,
rickettsiae, and viruses. Antibiotics are most effective against
bacteria and rickettsiae, and with no direct effect on viruses.
"Streptomycetes" (Streptomycetaceae; actinobacteria) is a family
of oxygen-utilizing (aerobic) bacteria that form chains or
filaments with occasional branches, the form giving the
appearance of microscopic fungi. They mostly live in soil, and
they are responsible for several types of human infections. Some
species produce antibiotics. "Rickettsiae" are a type of small
bacteria that usually occur in the cytoplasm of cells of lice,
fleas, ticks, and mites. Some species of rickettsiae are
parasitic in humans, causing epidemic typhus, murine typhus,
Rocky Mountain spotted fever, and other diseases.
... ... *commensal enteric Enterobacteriaceae: In general, the
term "commensal" refers to a symbiotic relationship in which one
species derives benefit and the other is unharmed. The term
"enteric" means relating to the intestine. The term "enteric
Enterobacteriaceae", in this context, refers to a type of
bacteria that occurs in the intestines and feces of man and
animals. The so-called "type genus" of the large family
Enterobacteriaceae is the familiar species Escherichia coli, a
common inhabitant of the human intestinal tract, with most
varieties of E. coli commensal in the intestinal tract. [Note:
Certain varieties of E. coli which are not pathogenic in the
intestine can be virulently pathogenic in other tissues of the
body. Conversely, there are varieties of E. coli which are
usually pathogenic _inside_ the intestinal tract and cause
serious diseases (e.g., various diarrheal diseases). The notion
that E. coli is a harmless human symbiont is inexact.]
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 29Oct99
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
EMERGENCE OF VANCOMYCIN RESISTANCE IN STAPHYLOCOCCUS AUREUS
The bacterial genus Staphylococcus has at least 30 different
species. The organisms are spherical cells approximately 1 micron
in diameter. They are nonmotile, they do not form *spores, and
they are ordinarily destroyed by *penicillin. One of the
staphylococcus species of clinical importance in humans is
Staphylococcus aureus, which is a major pathogen. The other two
staphylococcus species of clinical importance are *S. epidermidis
and *S. saprophyticus. S. aureus produces the enzyme coagulase,
which clots oxalated or citrated plasma, and the "coagulase test"
is a common test to differentiate S. aureus from other
staphylococcal infections: S. aureus is "coagulase-positive".
Almost every person will have some type of S. aureus infection
during a lifetime, ranging in severity from food poisoning or
minor skin infections to severe life-threatening infections. S.
aureus is one of the most common causes of community-acquired
infections and infections acquired in hospitals (*nosocomial
infections). S. aureus is also the most common cause of surgical
wound infections, and a major cause of nosocomial bloodstream
infection. After the initial success of penicillin in treating S.
aureus infections during and immediately after World War II,
bacterial resistance to penicillin began to emerge, and at the
present time, 70 to 80 percent of S. aureus isolates are
resistant to this antibiotic. *Methicillin and other
semisynthetic penicillins were successful in treating penicillin-
resistant S. aureus infections until the 1980s, when methicillin-
resistant S. aureus became *endemic in many hospitals. Since the
emergence of methicillin-resistant S. aureus, the *glycopeptide
vancomycin has been the only uniformly effective treatment for
staphylococcal infections. The recent emergence of glycopeptide
resistance in coagulase-negative staphylococci has heightened
concern about whether S. aureus could acquire glycopeptide
resistance. In May 1996, the world's first documented clinical
infection due to S. aureus with intermediate resistance to
glycopeptides (denoted as "glycopeptide-intermediate S. aureus")
was diagnosed in a patient in Japan [*Note #1].
... ... T.L. Smith et al (11 authors at 3 installations, US) now
report the first documented glycopeptide-intermediate S. aureus
infections in the US, two cases at two different installations in
Michigan and New Jersey. The authors conclude: "The emergence of
S. aureus with intermediate glycopeptide resistance threatens to
return us to the era before the development of antibiotics. To
prevent further emergence of S. aureus strains with intermediate
glycopeptide resistance, and the emergence of S. aureus with full
vancomycin resistance, the use of vancomycin must be optimized,
laboratory methods for the detection of resistant pathogens must
be enhanced, and infection-control precautions must be strictly
followed for infected or colonized patients."
-----------
Editor's note: In addition to the background material below, see
the SW Focus Report "Microbial Drug Resistance" available at URL
http://scienceweek.com/swfr013.htm
-----------
T.L. Smith et al: Emergence of vancomycin resistance in
Staphylococcus aureus.
(New England J. Med. 18 Feb 99 340:493)
QY: Michele L. Pearson, Hospital Infections Program, Centers for
Disease Control and Prevention, Atlanta, GA 30333 US.
-----------
Text Notes:
... ... *spores: Certain types of bacteria form spores,
specialized structures that may allow survival in extreme
environments and facilitate dissemination. The spore remains
dormant, nonreplicating, until appropriate environmental
conditions cause a transformation back to a viable replicating
organism.
... ... *penicillin: (penicillins) The penicillin antibiotics are
derived from molds of the genus Penicillium and obtained by
extraction of submerged cultures grown in special media. The most
widely used natural penicillin is Penicillin G. In general, with
6-aminopenicillanic acid as the fundamental chemical entity, an
almost unlimited variety of penicillin compounds can be
synthesized by coupling different radical carboxyl groups to the
free amino group.
... ... *S. epidermidis: This species of staphylococcus is the
primary cause of infections due to implanted appliances and
devices.
... ... *S. saprophyticus: This species of staphylococcus is a
relatively common cause of urinary tract infections in young
women.
... ... *nosocomial infections: In general, a nosocomial
infection is any infection acquired by a patient as a result of
entrance into a hospital. It is estimated that some 15 to 20
percent of all hospital workers carry S. aureus on the skin of
their hands, and that 60 to 70 percent of all hospital workers
carry S. aureus in their nostrils.
... ... *Methicillin: A "semisynthetic" penicillin antibiotic
(i.e., the basic penicillin structure is derived from the mold
Penicillium). It is less potent than Penicillin G.
... ... *endemic: (enzootic) An "endemic" disease is a disease
that prevails continually in a region, as opposed to an
"epidemic" disease, which is a disease with a relatively abrupt
sporadic outbreak.
... ... *glycopeptide: Any compound containing sugar(s) linked to
amino acids (or peptides), with the peptides preponderant. Such
compounds are an important component of bacterial cell walls.
The glycopeptide vancomycin, which is markedly bactericidal for
staphylococci, has a molecular weight of 1450 and is produced by
the bacterium Streptomyces orientalis.
... ... *Note #1: There are a number of different mechanisms that
can be evolved by microorganisms to cause resistance to drugs: 1)
Production of enzymes that destroy the active drug. 2) A change
in cell wall and/or membrane permeability to the drug. 3)
Development of an altered structured target for the drug. 4)
Development of an altered metabolic pathway that bypasses the
reaction inhibited by the drug. 5) Development of an altered
enzyme that can still perform its metabolic function but is much
less affected by the drug. Staphylococci resistant to Penicillin
G produce an enzyme (a beta-lactamase) that destroys the
antibiotic.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 21May99
-------------------
Related Background:
ON THE RESISTANCE OF BACTERIA TO ANTIBIOTICS
S. Levy (Tufts University, US), in a review of recent
developments in antibiotic resistance, notes that strains of at
least 3 pathogenic bacterial species -- Enterococcus faecalis,
Mycobacterium tuberculosis, Pseudomonas aeruginosa -- have
already developed resistance to every one of the 100 antibiotic
drugs in use by clinicians. Levy says a change in attitudes of
the public and clinicians concerning the overuse of antibiotics
is badly needed, and that a reversal of increasing bacterial
resistance to antibiotics, as well as increasing resistance of
parasites, fungi, and viruses to antimicrobials and antivirals,
will require a new global awareness of the broad consequences of
anti-pathogen drug usage.
QY: Stuart B. Levy, Tufts Univ. School of Medicine 617-636-6571
(Scientific American March 1998) (Science-Week 20 Feb 98)
-------------------
Related Background:
STUDIES SHOW MARKED INCREASE IN DRUG RESISTANCE OF MICROBES
Widespread use of antibiotics continues to force the evolution of
strains of pathogens resistant to the drugs. For example, the
incidence in the U.S. of microbes resistant to penicillin has
increased fourfold since 1994. At the May 19th International
Conference of the American Lung Association and American Thoracic
Society in San Francisco, researchers from the State University
of New York (Buffalo NY US) and the University of Iowa College of
Medicine (Iowa City IA US) found the increase in resistance of
Streptococcus pneumoniae, a common cause of respiratory
infections, to be dramatic. 10.5% of the samples were highly
resistant to antibiotics and 24.9% moderately resistant. In 1994,
those figures stood at only 3.2% and 14.1%, respectively. In the
Southeastern part of the U.S., 41% of the samples were found to
be resistant. The researchers suggest that the medical community
must be on the watch for rapidly developing epidemics caused by
antibiotic resistant strains of pathogens, and that antibiotics
themselves should be administered only when necessary if we are
to slow down the evolution of these resistant microbes.
(UPI 19 May 97) (Science-Week 22 May 97)
-------------------
Related Background:
APPEARANCE OF A STAPHYLOCOCCUS STRAIN RESISTANT TO VANCOMYCIN
Staphylococcus aureus is a common pathogenic bacterium in
hospitals, and causes thousands of often fatal infections each
year. Vancomycin is an antibiotic of last resort, which is used
when all other antibiotics fail. Now the first case has appeared
in Japan of a 4 year old boy infected with a strain of
Staphylococcus aureus resistant to vancomycin. Health experts
say it is only a matter of time before the pathogen reaches U.S.
hospitals. Fred Tenover, laboratory chief of the U.S. Center for
Disease Control Hospital Infections Branch says, "The strain is
marching up the ladder of resistance... It is not a cause for
panic, but it is a cause for concern."
(UPI 28 May 97) (Science-Week 29 May 97)
-------------------
Related Background:
REDUCED ANTIBIOTIC USAGE LOWERS BACTERIAL RESISTANCE
To understand the mechanism of the worldwide increase in
bacterial resistance to antibiotics one need only consider that
for all biological organisms most chemical aspects are more or
less displayed as a Gaussian distribution, the so-called "normal"
or "bell-shaped" curve. What this means in the context of
applying an antibiotic to a population of a particular bacterial
species is that something like 10% or 15% of the population will
show much lower than average resistance to the drug, about 60%
will have close to the average resistance to the drug, and about
10% to 15% will show above average resistance to the drug, all
because of the way the chemistry responsible for resistance to
the drug is distributed in the population. These numbers are
variable from one species of bacteria to another, and they also
vary with the antibiotic used, but the general idea is the same.
The result of all of this is that if we use an antibiotic against
a specific bacterial population, those members of the population
that have superior resistance to the antibiotic will survive to
reproduce their genome, most of the others will be killed, and
before long we will have on our hands populations of that species
which are more or less totally resistant to the antibiotic. This
is nothing more than a concrete instance of the idea of
"selection pressure" in evolution. In 1946 about 90% of
Staphylococcus aureus (a common and dangerous pathogen bacterium)
in hospitals were killed by the antibiotic penicillin, which
first became widely available at about that time. By only 6 years
later, 75% of S. aureus caught and cultured in hospitals were
resistant to penicillin, and by the 1970s, 90% of S. aureus,
whether in hospitals or in the community, were resistant to the
drug. There are similar stories concerning other bacterial
species and other drugs, the worst scenarios evidently occurring
in hospitals; but one cannot fault hospitals, because in both
hospitals and the community antibiotics have been routinely
needlessly administered and/or over-administered, with a
consequent selection pressure that produces antibiotic-resistant
pathogens. Can the process be reversed? There may still be some
hope against bacterial species which are not already
overwhelmingly resistant. This week Helena Seppala et al (about
100 authors in FI) report that in Finland, after an organized
nationwide reduction in the use of macrolide antibiotics
(macrolides are large-ring molecules with many functional side
groups) for outpatient therapy, the resistance of group A
streptococci to the common antibiotic erythromycin dropped by
half from 16.5 per cent in 1992 to 8.5 per cent in 1996. In an
editorial in the New England Journal of Medicine, Morton N.
Swartz (Massachusetts General Hospital, Boston US) calls this "an
impressive example of how an enlightened national policy on
antibiotic use can become an effective public health measure."
QY: H. S. Seppala, Antimicrobial Research Laboratory, PO Box 57,
20521 Turku, FI.
(New England J. Med. 14 Aug 97) (Science-Week 15 Aug 97)
-------------------
NEW MULTI-DRUG RESISTANCE OF PLAGUE PATHOGEN
Plague, also called bubonic plague or "Black Death", is a disease
with a notorious history. It is caused by the bacillus Yersinia
pestis, which infects wild rodents. The bubonic variant of the
disease is transmitted to humans from rodents by the bite of an
infected flea. Human to human transmission occurs by inhalation
of respiratory droplets spread by the cough of patients with
plague who have developed pulmonary lesions, and the result of
this is "primary pneumonic plague", which differs from "bubonic
plague" in that bubonic plague affects the lymph nodes, among
other tissues (producing "buboes", lymph node swellings). The
last plague pandemic began in Hong Kong in 1894 and spread
throughout the world. Plague still exists as an endemic disease
in many parts of the world, including the southwestern U.S.
Prevention of plague is based on rodent control, and the use of
insect repellents to minimize flea bites. Early treatment after
infection with the antibiotics streptomycin, chloramphenicol, or
tetracycline reduces mortality to less than 5%. Nevertheless,
plague is now considered a reemerging disease, with recent
epidemics in a number of countries after an absence of as much as
3 decades. The incidence of the disease has also been spreading
in the U.S. Now Marc Galimand et al (World Health Organization
and the Pasteur Institute, FR) report high-level resistance of Y.
pestis in a clinical isolate in Madagascar to multiple
antibiotics, including resistance to all the drugs recommended
for plague prophylaxis and therapy. The resistant genes are
apparently carried by a plasmid that can conjugate to other Y.
pestis isolates. So this pathogen species, heretofore considered
universally susceptible to antibiotics, is now exhibiting high
and spreadable resistance to these drugs. Epidemiologists are
alarmed and are urging an international effort to deal with the
problem.
QY: Elisabeth Carniel, Institut Pasteur, 28 rue du Dr.
Roux, 75724 Paris CEDEX 15, FR.
(New England J. Med. 4 Sep 97) (Science-Week 12 Sep 97)
-------------------
APPARENT IRREVERSIBILITY OF BACTERIAL ANTIBIOTIC RESISTANCE
At a recent meeting of the European Society for Evolutionary
Biology (Arnhem NL), several research groups have apparently
independently confirmed the unhappy news that bacteria that have
mutated to exhibit resistance to specific antibiotics do not
evolve susceptible strains when they are no longer exposed to
these antibiotics. Bruce Levin and Bassam Tomah (Emory
University, US) report that 25% of bacteria sampled from infant
diapers are strains of E. coli still resistant to the antibiotic
streptomycin, which has been rarely used during the past 30
years. Richard Lenski (Michigan State University, US) has
independently shown that after 20,000 generations in the absence
of streptomycin, E. coli still carries the gene that confers
resistance to the antibiotic. The consensus is apparently that a
compensatory mutation has occurred, a mutation that compensates
for the loss of fitness produced by the gene that confers
antibiotic resistance, and which results in long-term survival of
the resistant strain. Levin suggests the same kind of
compensatory mutations "will almost certainly be found in other
resistant bacteria." The implication is that the evolutionary
development of bacterial resistance to antibiotics will not be
reversed by reducing the use of these antibiotics, which means
the effectiveness of these antibiotics is essentially
irreversibly lost.
QY: B. Levin, Emory Univ., Population Genetics (404) 727-5660
(Science 24 Oct 97) (Science-Week 14 Nov 97)
For more information: http://scienceweek.com/swfr.htm
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2. MEDICAL BIOLOGY: ON NEURODEGENERATIVE DISEASES AND PRIONS
Prions are a class of poorly understood proteins implicated
in a number of exotic human neurological diseases and in some
common animal diseases such as sheep scrapie and bovine
spongiform encephalopathy in cattle ("mad cow disease").
Spongiform encephalopathies are a type of brain disease found in
humans and animals and are characterized by macroscopic vacancies
produced by the disease process (the brain has a sponge-like
appearance). What is remarkable about prions is that they behave
as infectious agents, but they are 100 times smaller than viruses
and their mechanism of replication is unclear. One human disease
in which prions have been strongly implicated is *Creutzfeldt-
Jakob disease (CJD), which appears to have a genetic basis in
about 15% of the cases. All the prion diseases are apparently
associated with the accumulation in the brain of an abnormal
*protease-resistant isoform of the prion protein. In other words,
an abnormal variant of the normal prion protein is somehow copied
or produced by the disease process, which can be initiated by
introducing infectious prion into the system.
The term "amyloid" ("starch-like") refers to a variety of
polypeptide molecules defined by their properties, particularly
by their tendency to arrange in a twisted *beta-pleated fibrillar
structure. Amyloid is in general a proteinaceous material,
deposits of which have been classically noted to occur in the
brains of *Alzheimer's disease and older *Down syndrome patients,
and to a much lesser degree, in association with normal aging.
Amyloid material consists primarily of a highly aggregated
42-amino acid polypeptide called "beta-amyloid".
In general, a "somatic mutation" is a mutation occurring in
non-germ cells, which means the mutation is not transmitted to
the next generation. In contrast, a "germ-line mutation" is a
mutation occurring in germ cells, and is thus transmitted to the
next generation.
In this context, the term "sporadic" means non-familial.
In 1997 Stanley B. Prusiner was awarded the Nobel Prize in
Physiology or Medicine for his discovery of prions, an entirely
new genre of disease-causing agents.
... ... Stanley B. Prusiner (University of California San
Francisco, US) presents a review of current research on the role
of prions in neurodegenerative diseases, the author making the
following points:
1) The author points out that Alzheimer's disease is the
most common neurodegenerative disorder, with approximately 4
million people in the US having this disease. In the US at
present, approximately 1 million people have *Parkinson's
disease. Much less common are *frontotemporal dementia (40,000
people), *Huntington's disease (30,000 people), *amyotrophic
lateral sclerosis (20,000 people), and *spinocerebellar ataxia
(12,000 people), and prion diseases (400 people). Among persons
who are 60 years of age, the prevalence of Alzheimer's disease is
approximately 1 in 10,000, but among those who are 85 years of
age, the prevalence is greater than 1 in 3. These data suggest
that by 2025, there will be more than 10 million cases of
Alzheimer's disease in the US, and by 2050, the number will
approach 20 million. The current annual cost associated with
Alzheimer's disease in the US is estimated at $200 billion. Age
is also the most important risk factor for Parkinson's disease,
with at least 50 percent of persons who are 85 years of age
having at least one symptom or sign of parkinsonism.
2) The author points out that nearly all neurodegenerative
disorders involve abnormal processing of neuronal proteins. The
aberrant mechanism can involve a misfolding of proteins, altered
*post-translational modification of newly synthesized proteins,
abnormal *proteolytic cleavage, anomalous *gene splicing,
improper gene expression, or diminished clearance of degraded
protein. Misprocessed proteins often accumulate because the
cellular mechanisms for removing them are ineffective, and the
particular protein that is improperly processed determines the
malfunction of distinct sets of neurons and thus the clinical
manifestation of the disease.
3) The author points out that prions are infectious
proteins. In mammals, prions replicate by recruiting normal
cellular prion protein and stimulating its conversion to the
disease-causing prion isoform ("scrapie prion"; Prp[supSC]). A
major feature that distinguishes prions from viruses is that
scrapie prion can be encoded by a chromosomal gene resulting from
a mutation of the normal prion gene. Limited proteolysis of
scrapie prion produces a smaller and protease-resistant molecule
of approximately 142 amino acids which polymerizes into amyloid.
4) The author points out that the polypeptide chains of
normal prion and scrapie prion are identical in composition but
differ in their 3-dimensional folded structures. Normal prion is
rich in spiral-like formations of amino acids (alpha-helices) and
has little flattened strands (beta-sheets) of amino acids,
whereas scrapie prion is less rich in alpha-helices and has much
more beta-sheet domains. There is evidence that normal prion has
3 alpha-helices and 2 short beta-strands; in contrast, a
plausible model suggests that scrapie prion may have only 2
alpha-helices and more beta-strands. This structural transition
from alpha-helices to beta-sheet in prion protein is apparently
the fundamental event underlying prion disease.
5) The author points out that four new concepts have emerged
from studies of prions:
... ... a) Prions are the only known example of infectious
pathogens that are devoid of nucleic acid. All other infectious
agents have genomes composed of either RNA or DNA that direct the
synthesis of their progeny.
... ... b) Prion diseases may be manifested as infectious,
genetic, or sporadic disorders. No other group of illnesses with
a single cause has such a wide spectrum of clinical
manifestations.
... ... c) Prion diseases result from the accumulation of scrapie
prion, which has a substantially different molecular conformation
from that of its precursor, normal prion.
... ... d) Scrapie prion can have a variety of conformations,
each of which seems to be associated with a specific disease. How
a particular conformation of scrapie prion is imparted to normal
prion during replication in order to produce a nascent scrapie
prion with that conformation is unknown. The factors that
determine the site in the central nervous system where a
particular scrapie prion is deposited are also not known.
6) The author tabulates the known pathogenic features of
known prion diseases as follows:
... ... a) *Kuru: Human hosts, "Fore" people in New Guinea.
Infection occurs via ritualistic cannibalism.
... ... b) Creutzfeldt-Jakob disease:
... ... ... Via medical procedures (iatrogenic): Human hosts.
Infection from prion-contaminated human *growth hormone, *dura
mater grafts, etc.
... ... ... *New variant: Human hosts. Possible infection from
bovine prions.
... ... ... Familial: Human hosts. Results from germ-line
mutations in the prion gene.
... ... ... Sporadic: Human hosts. Results from somatic mutation
or spontaneous conversion of normal prion into scrapie prion.
... ... c) *Gerstmann-Straeussler-Scheinker disease: Human hosts.
Results from germ-line mutations in the prion gene.
... ... d) *Fatal familial insomnia: Human hosts. Results from
germ-line mutations in the prion gene.
... ... e) *Scrapie: Sheep hosts. Results from infection in
genetically susceptible sheep.
... ... f) Bovine spongiform encephalopathy: Cattle hosts.
Results from infection with prion-contaminated meat and bone
meal.
... ... g) Transmissible mink encephalopathy: Mink hosts. Results
from infection with prion from sheep or cattle.
... ... h) Chronic wasting disease: Mule, deer, elk hosts.
Mechanism of pathogenesis unknown.
... ... i) Feline spongiform encephalopathy: Cat hosts. Results
from infection with prion-contaminated beef.
... ... j) Exotic *ungulate encephalopathy: Greater kudu, nyala,
oryx hosts. Results from infection with prion-contaminated meat
and bone meal.
7) Concerning the general paradigm that virtually all
neurodegenerative disorders involve abnormal processing of
neuronal proteins, the author states: "It is tempting to
speculate that abnormal processing of neuronal proteins also
occurs in other diseases of the central nervous system, such as
schizophrenia, bipolar disorders, autism, and narcolepsy. Most
cases of these diseases are sporadic, but a substantial minority
appear to be familial."
8) The author concludes: "Over the past two decades,
remarkable progress has been made in elucidating the causes of
neurodegenerative diseases, and the time has come to intensify
the search for drug targets and for compounds that interrupt the
disease processes. Drugs that block the mishandling of a
particular protein may be most effective for certain disorders;
for others, drugs that enhance the clearance of an aberrant
protein or fragment may prove most useful. Regardless of the
therapeutic approach, accurate, early detection of
neurodegeneration will be extremely important so that drugs can
be given before substantial damage to the central nervous system
has occurred. However, the enormity of these tasks -- developing
useful diagnostic tests and discovering effective therapies --
should not be underestimated."
-----------
Stanley B. Prusiner: Shattuck lecture -- Neurodegenerative
diseases and prions.
(New England J. Med. 17 May 01 344:1516)
QY: Stanley B. Prusiner: Box 0518, University of California, San
Francisco, CA 94143-0518 (US).
-----------
Text Notes:
... ... *Creutzfeldt-Jakob disease (CJD): Until 30 years ago,
Creutzfeldt-Jakob disease was an obscure form of dementia unknown
to most physicians. The name is now familiar to the medical
community as the major prion disease in humans.
... ... *protease: In general, any enzyme that cleaves proteins,
usually by hydrolysis.
... ... *beta-pleated: In general, protein chains fold into
alpha-helices or beta-sheet structures. The beta-sheet is a
protein structure where the peptide is extended and stabilized
by hydrogen bonding between NH and CO groups of different
polypeptide chains or of separate regions of the same chain.
... ... *Alzheimer's disease: There are various forms of dementia
produced by various causes. Alzheimer-type dementia (Alzheimer's
disease) is apparently related to what appear to be specific
cellular and histological degenerative processes, with loss of
cells from several specific brain areas, the brain showing
moderate to marked atrophy. Memory loss is the most prominent
early symptom.
... ... *Down syndrome: A birth defect marked by mental
retardation and many physical defects, the syndrome arising from
an extra chromosome 21 (trisomy 21).
... ... *Parkinson's disease: A neurological disorder first
described by James Parkinson (1817) and associated with
degeneration of a specific small region of the brain and a
resultant loss of projection to several important brain centers.
One must distinguish "parkinsonism" from Parkinson's disease.
Parkinsonism is a syndrome (a complex of symptoms; in this
context, a complex of various movement symptoms) that may be
caused by Parkinson's disease, but which may also be caused by
infectious, vascular, pharmacological, toxic, metabolic,
structural, and various degenerative disorders.
... ... *frontotemporal dementia: Dementia associated with loss
of functions associated with the frontotemporal lobes of the
brain.
... ... *Huntington's disease: (Huntington's chorea) First
described by George Huntington (1850-1916), the disease attacks
specific regions of the brain (e.g., caudate nucleus and
putamen), and leads to insanity and eventual death.
... ... *amyotrophic lateral sclerosis: A progressive disease of
motor neurons (spinal cord nerve cells that control voluntary
muscles). 50 percent of patients die within 3 years of the first
symptoms.
... ... *spinocerebellar ataxia: In general, an ataxia is an
inability to coordinate muscle activity during voluntary
movement. Spinocerebellar ataxia is the most common hereditary
ataxia. The spinocerebellar degenerative disorders are a group of
diseases involving neurons in several nervous system structures,
including the spinal cord and cerebellum.
... ... *post-translational: In this context, translation is
protein synthesis, the process during which polypeptides are
synthesized in accordance with RNA code.
... ... *proteolytic: In general, "proteolysis" is the
enzyme-catalyzed degradation of protein by hydrolysis of one or
more peptide bonds.
... ... *gene splicing: In this context, the production of new
genes by an abnormal replication process that combines fragments
of DNA in new arrangements.
... ... *Kuru: This disease is similar to Creutzfeldt-Jakob
disease, and is a human spongiform encephalopathy. Kuru occurs
only in the easter highlands of New Guinea, occurs more
frequently in women than in men, which apparently coincides with
the customs surrounding cannibalism in a society where the
remains of dead relatives are handled and eaten primarily by
children and women. After cannibalism was outlawed, the incidence
of the disease decreased, and the current consensus is that
cannibalism was the primary mode of transmission of the
pathological agent.
... ... *growth hormone: A vertebrate polypeptide hormone that
regulates growth. In general, hormones are signaling molecules
secreted into the blood stream by endocrine cells and acting on
target cells that possess receptors for the hormone.
... ... *dura mater: In this context, a thick protective membrane
that surrounds the brain. There is also a dura mater surrounding
the spinal cord.
... ... *New variant: In 1996, the new variant of Creutzfeldt-
Jakob disease (new-variant CJD) was recognized in the UK
population, primarily in younger people, the new disease with
distinctive pathological characteristics similar to those seen in
macaque monkeys infected with the agent of bovine spongiform
encephalopathy.
... ... *Gerstmann-Straeussler-Scheinker disease: A slowly
progressive neurodegenerative genetic disease similar to
Creutzfeldt-Jakob disease and transmissible to experimental
animals. The disease is much rarer than Creutzfeldt-Jakob disease
and has an earlier onset.
... ... *Fatal familial insomnia: insomnia: Another familial form
of Creutzfeldt-Jakob disease. This very rare disease is difficult
to transmit to experimental animals. The age of onset varies
widely, the course of the disease averaging 13 months. (Note: All
the human spongiform encephalopathies are invariably fatal.)
... ... *Scrapie: Susceptibility to scrapie varies among
different breeds of sheep, with goats 100 percent susceptible.
The disease is transmissible to laboratory monkeys, mice, and
hamsters.
... ... *ungulate: In general, a hoofed mammal.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 18May01
For more information: http://scienceweek.com/swfr.htm
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3. PHYSIOLOGY:
ON THE ACCURACY OF SOUND LOCALIZATION IN AN INSECT
Humans use at least two different strategies to localize the
horizontal position of sound sources, depending on the
frequencies in the stimulus. For frequencies below 3000 hertz,
interaural time differences are used to localize the source;
above these frequencies, interaural intensity differences are
used as cues. The longest interaural time differences in humans,
which are produced by sounds arising directly lateral to one ear,
are on the order of only 700 microseconds (the width of the head
divided by the speed of sound in air). Experiments, however,
demonstrate that humans can actually detect interaural time
differences as small as 10 microseconds, and this sensitivity
translates into an accuracy for sound localization of
approximately 1 degree.
The term "parasitoid" refers to organisms, especially
insects, that introduce their eggs into another animal, the eggs
hatching and larvae developing in a slow and controlled manner
using the resources of the host without killing it. At
maturation, the parasitoid emerges and usually does cause the
death of the host.
... ... A.C. Mason et al (3 authors at Cornell University, US)
present a report of hyperacute directional hearing in a
microscale insect auditory system, the authors making the
following points:
1) The authors point out that the physics of sound
propagation imposes fundamental constraints on sound
localization: for a given frequency, the smaller the receiver,
the smaller the available cues. Thus, the creation of nanoscale
acoustic microphones with directional sensitivity is very
difficult. The fly Ormia ochracea possesses an unusual "ear" that
largely overcomes these physical constraints, and attempts to
exploit principles derived from O. ochracea for improved hearing
aids are now in progress.
2) The authors point out that O. ochracea (Diptera:
Tachinidae) is a parasitoid fly, with egg-laying (gravid) female
flies locating their hosts, male crickets, by homing in on the
loud and persistent songs of the crickets. Because of its small
body size (less than 1 centimeter in any aspect), this fly must
deal with extremely small interaural difference cues to guide
directional hearing. The calling song of the host cricket is an
amplitude-modulated 5000 hertz tone (6.8 centimeter wavelength).
The distance between the eardrums of the fly is approximately 0.5
millimeters, which means that 5 kilohertz sound waves are not
diffracted by the body of the fly and generate no interaural
intensity difference (indeed, none can me measured). The
interaural time difference is frequency independent and depends
only on the speed of sound and the distance between the two ears.
The maximal interaural time difference in this fly at 90 degrees
azimuth is 1.5 microseconds and decreases to zero for a sound
source on the midline axis. This minuscule interaural time
difference is the only physical cue available for computation of
source direction. Nevertheless, this fly can reliably localize
cricket song both in nature and in the laboratory.
3) The authors report experiments that demonstrate that O.
ochracea can behaviorally localize a salient sound source with a
precision equal to that of humans. Despite its small size and
minuscule interaural cues, the fly localizes sound sources to
within 2 degrees azimuth. As the eardrums of the fly are less
than 0.5 millimeters apart, localization cues are of the order of
50 nanoseconds. Directional information is represented in the
fly's auditory system by the relative timing of receptor
responses in the two ears, and low-jitter, phasic receptor
responses are pooled to achieve hyperacute time-coding.
4) The authors suggest that the principle evolutionary
innovation responsible for the ability of this fly to overcome
its unfavorable auditory physics is a pair of anatomically and
functionally couple eardrums. The mechanical resonance of the
fly's peripheral auditory apparatus in a directional sound field
transforms the minuscule time delay in the free field into two
cues that can used by its nervous system: a) the interaural time
delay between the eardrums is increased from a maximum of 1.5
microseconds to approximately 55 microseconds; b) the vibration
amplitude difference between the two eardrums is as much as 10
decibels for sound sources at 45 to 90 degrees azimuth. Thus,
minute interaural time differences in the sound field are
converted by eardrum mechanics to interaural differences that are
process by the nervous system.
5) The authors suggest these results demonstrate that
nanoscale/microscale directional microphones patterned after the
fly O. ochracea have the potential for highly accurate
directional sensitivity independent of the size of the
microphones. In the fly itself this performance is dependent on a
newly discovered set of specific coding strategies employed by
the fly's nervous system.
-----------
A.C. Mason et al: Hyperacute directional hearing in a microscale
auditory system.
(Nature 5 Apr 01 410:686)
QY: Andrew C. Mason: amason@scar.utoronto.ca
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 18May01
For more information: http://scienceweek.com/swfr.htm
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4. THEORETICAL PHYSICS:
ON THE EQUILIBRIUM MECHANICAL PROPERTIES OF INDIVIDUAL MOLECULES
In general, conventional thermodynamics is the systematic
study of the relationship between heat, work, temperature, and
energy, and the relations of these variables to the general
behavior of systems at equilibrium. The term "classical
thermodynamics" usually refers to a phenomenological approach
that does not involve consideration of individual atoms or
molecules. "Statistical thermodynamics" does consider individual
atoms or molecules, in the sense of involving a few elementary
assumptions concerning atoms or molecules, but the focus in
statistical thermodynamics is on the behavior of statistical
populations of atoms or molecules. In general, statistical
thermodynamics attempts to express macroscopic thermodynamic
properties in terms of the statistics of the behavior of
individual particles and their interactions. During the 20th
century, there has emerged the field of "nonequilibrium"
("irreversible") thermodynamics. Unlike classical thermodynamics,
in which it is assumed that the system is at equilibrium,
nonequilibrium thermodynamics investigates systems that are not
at equilibrium. There has been much progress in nonequilibrium
thermodynamics, particularly for systems close to equilibrium,
but in general our understanding of nonequilibrium phenomena is
not comparable to our understanding of equilibrium phenomena.
Now suppose one has an individual molecule isolated and
under control, for example an individual polymer molecule
specifically constrained and contacted so that it can be
stretched, and one wants to describe (and understand) the
behavior of this single molecule, not in terms of electrons and
atomic nuclei and so on, but as a _single system_. A priori, one
can say that if the laws of thermodynamics are not constrained by
scale, they should in principle be applicable to a single
molecule considered as a thermodynamic system. And, in fact, it
should be possible to develop statistical considerations for a
single molecule if we consider the real fluctuating states of the
molecule as a statistical ensemble of states constrained by
thermodynamic parameters. This is the essential basis of research
applying statistical thermodynamics (both equilibrium and
nonequilibrium) to the behavior of individual molecules.
... ... G. Hummer and A. Szabo (National Institutes of Health,
US) present a theoretical analysis of nonequilibrium single-
molecule pulling experiments, the authors making the following
points:
1) The authors point out that recent advances in the
micromanipulation of single molecules have led to new insights
into the dynamics, interactions, structure, and mechanical
properties of individual molecules. Single-molecule manipulation
with an *atomic force microscope, *laser-tweezer stretching, and
analogous computer experiments have revealed details about
unfolding and unbinding events of individual proteins and their
complexes. In an atomic-force-microscope experiment, a single
molecule is subjected to a time-varying external force, e.g., by
pulling on the end of a linear polymer. The applied force is
determined from the time-dependent position of the cantilever tip
with respect to the sample. Thus, one can drive rare molecular
events, determine their force characteristics, and simultaneously
monitor them with atomic resolution. However, both experiments
and simulations actively perturb the system, leading to
hysteresis and nonequilibrium effects.
2) The authors ask: How can one extract equilibrium
properties from such measurements that drive the system away from
equilibrium? From the second law of thermodynamics, we know that
on average the mechanical work of pulling will be larger than the
free energy. Only if the experiment is performed reversibly,
i.e., infinitely slowly, will the work equal the free energy.
Thus, making rigorous thermodynamic measurements by pulling
appears to require an extrapolation to zero pulling speed.
However, C. Jarzynski (1997) recently discovered a remarkable
identity between thermodynamic free energy differences and the
irreversible work. This identity, although not directly
applicable to atomic force measurements, suggests that in
principle one should be able to extract free energy surfaces from
repeated pulling experiments.
3) The authors (Hummer and Szabo) demonstrate, with a
quantitative theoretical analysis, how equilibrium free energy
profiles can be extracted rigorously from repeated non-
equilibrium force measurements on the basis of an extension of
Jarzynski's identity between free energies and irreversible work.
... ... In a commentary on the above study, C. Jarzynski (Los
Alamos National Laboratory, US) makes the following points:
1) Jarzynski points out that what Hummer and Szabo propose
amounts to a distinctive method of deducing the equilibrium
mechanical properties of individual molecules. Hummer and Szabo
provide a prescription for combining the data from [repeated
pulling] experiments, so that what ultimately emerges is the
equilibrium tension as a function of elongation, even if the
molecule was driven away from equilibrium during the pulling
process. Jarzynski states: "Moreover, they make a solid case --
by using simulations as well as analysis of published
micromanipulation data -- that their method is experimentally
feasible."
2) Concerning the theoretical approach of Hummer and Szabo,
Jarzynski points out that when a system is perturbed away from
equilibrium by the arbitrary variation of an external parameter,
then a particular statistical description of its response -- the
description constructed via a weighting procedure involving a
Boltzmann distribution factor [*Note #1] -- behaves with
remarkable simplicity: it exactly follows the instantaneous
equilibrium state associated with the changing value of the
parameter. Jarzynski points out that Hummer and Szabo have
translated this abstract notion into a concrete proposal for an
experimental method of measuring the properties of molecules.
"Not only does their method represent a potentially useful
laboratory technique, but an experiment along these lines would
provide the first direct test of the underlying theory."
-----------
G. Hummer and A. Szabo: Free energy reconstruction from
nonequilibrium single-molecule pulling experiments.
(Proc. Natl. Acad. Sci. US 27 Mar 01 98:3658)
QY: Gerhard Hummer: hummer@helix.nih.gov
-----------
C. Jarzynski: How does a system respond when driven away from
thermal equilibrium?
(Proc. Natl. Acad. Sci. US 27 Mar 01 98:3636)
QY: C. Jarzynski: chrisj@lanl.gov
-----------
Text Notes:
... ... *atomic force microscope: An atomic force microscope is a
type of microscope in which a small probe is held on a spring-
loaded cantilever in contact with the surface of a sample. In
this context, single polymer molecules are anchored between a
surface and an atomic force microscope tip and then stretched.
until the molecule became detached.
... ... *laser-tweezer stretching: (optical-tweezer stretching)
The term "laser tweezers" refers to a laser trap used to hold and
move microscopic objects. The term "laser trap" refers to a
device for confining atoms, molecules, and neutral particles up
to 10 microns in diameter, the trap consisting of a focused laser
beam tuned to a frequency such that particles are attracted to
regions of high laser intensity.
... ... *Note #1: The weighting factor is e^(-W/kT), where (W) is
the total work performed, (k) is Boltzmann's constant, (T) is
absolute temperature.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 18May01
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
BIOPHYSICS: ATOMIC FORCE MICROSCOPY IN BIOLOGICAL RESEARCH
The new technology of scanning probe microscopy has created a
revolution in microscopy, with applications ranging from
condensed matter physics to biology. The first scanning probe
microscope, the scanning tunneling microscope, was invented by G.
Binnig and H. Rohrer in the 1980s (they received the Nobel Prize
in Physics in 1986), and the invention has been the catalyst of a
technological revolution. Scanning probe microscopes have no
lenses. Instead, a "probe" tip is brought very close to the
specimen surface, and the interaction of the tip with the region
of the specimen immediately below it is measured. The type of
interaction measured essentially defines the type of scanning
probe microscopy. When the interaction measured is the force
between atoms at the end of the tip and atoms in the specimen,
the technique is called "atomic force microscopy". When the
*quantum mechanical tunneling current is measured, the technique
is called "scanning tunneling microscopy". These two techniques,
atomic force microscopy (AFM) and scanning tunneling microscopy
(STM) have been the parents of a variety of scanning probe
microscopy techniques investigating a number of physical
properties.
... ... C. Wright-Smith and C.M. Smith (San Diego State College,
US) present a review of the use of atomic force microscopy in
biology, the authors making the following points:
1) Since its introduction in the 1980s, atomic force
microscopy (ATM) has gained acceptance in biological research,
where it has been used to study a broad range of biological
questions, including protein and DNA structure, protein folding
and unfolding, protein-protein and protein-DNA interactions,
enzyme catalysis, and protein crystal growth. Atomic force
microscopy has been used to literally dissect specific segments
of DNA for the generation of genetic probes, and to monitor the
development of new gene therapy delivery particles.
2) Atomic force microscopy is just one of a number of novel
microscopy techniques collectively known as "scanning probe
microscopy (SPM). In principle, all SPM technologies are based on
the interaction between a submicroscopic probe and the surface of
some material. What differentiates SPM technologies is the nature
of the interaction and the means by which the interaction is
monitored.
3) Atomic force microscopy produces a topographic map of the
sample as the probe moves over the sample surface. Unlike most
other SPM technologies, atomic force microscopy is not dependent
on the electrical conductivity of the product being scanned, and
ATM can therefore in ambient air or in a liquid environment, a
critical feature for biological research. The basic atomic force
microscope is composed of a stylus-cantilever probe attached to
the probe stage, a laser focused on the cantilever, a photodiode
sensor (recording light reflected from the cantilever), a digital
translator recorder, and a data processor and monitor.
4) Atomic force microscopy is unlike other SPM technologies
in that the probe makes physical (albeit gentle) contact with the
sample. The cornerstone of this technology is the probe, which is
composed of a surface-contacting stylus attached to an elastic
cantilever mounted on a probe stage. As the probe is dragged
across the sample, the stylus moves up and down in response to
surface features. This vertical movement is reflected in the
bending of the cantilever, and the movement is measured as
changes in the light intensity from a laser beam bouncing off the
cantilever and recorded by a photodiode sensor. The data from the
photodiode is translated into digital form, processed by
specialized software on a computer, and then visualized as a
topological 3-dimensional shape.
-----------
C. Wright-Smith and C.M. Smith: Atomic Force Microscopy.
(The Scientist 22 Jan 01)
QY: Carol Wright-Smith: csmith@sdsc.edu
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 2Feb01
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
ON SCANNING PROBE MICROSCOPY
... ... A. Yazdani and C.M. Lieber (2 installations,
US) present a review of recent developments in scanning probe
microscopy, the authors making the following points:
1) The invention and development of scanning probe
microscopy has taken the ability to image matter to the atomic
scale and opened fresh perspectives on everything from
semiconductors to biomolecules, and new methods are being devised
to modify and measure the microscopic landscape in order to
explore its physical, chemical, and biological features.
2) In scanning tunneling microscopy, electrons quantum
mechanically "tunnel" between the tip and the surface of the
sample. This tunneling process is sensitive to any overlap
between the electronic wave functions of the tip and sample, and
depends exponentially on their separation. The scanning tunneling
microscope makes of this extreme sensitivity to distance. In
practice, the tip is scanned across the surface, while a feedback
circuit continuously adjusts the height of the tip above the
sample to maintain a constant tunneling current. The recorded
trajectory of the tip creates an image that maps the electronic
wave functions at the surface, revealing the atomic landscape in
fine detail.
2) The most widely used scanning probe microscopy technique,
one which can operate in air and liquids, is atomic force
microscopy. In this technique, a tip is mounted at the end of a
soft cantilever that bends when the sample exerts a force on the
tip. By optically monitoring the cantilever motion it is possible
to detect extremely small chemical, electrostatic, or magnetic
forces which are only a fraction of those required to break a
single chemical bond or to change the direction of magnetization
of a small magnetic grain. Applications of atomic force
microscopy have included in vitro imaging of biological
processes.
3) In general, the various techniques of scanning probe
microscopy have now been applied to high-resolution spectroscopy,
the probing of nanostructures, measurements of forces in
chemistry and biology, the production of deliberate movements of
small numbers of atoms, and the use of precision lithography as a
tool for making nanometric-sized electronic devices.
4) The authors conclude: The scanning probe microscope has
evolved from a passive imaging tool into a sophisticated probe of
the nanometer scale. These advances point to exciting
opportunities in many areas of physics and biology, where
scanning probe microscopes can complement macroscopically
averaged measurement techniques and enable more direct
investigations. More importantly, these tools should inspire new
approaches to experiments in which controlled measurements of
individual molecules, molecular assemblies, and nanostructures
are possible."
-----------
A. Yazdani and C.M. Lieber: Up close and personal to atoms.
(Nature 16 Sep 99 401:227)
QY: Ali Yazdani [ayazdani@uiuc.edu]
-----------
Text Notes:
... ... *quantum mechanical tunneling current: In general,
quantum mechanical 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.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 29Oct99
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
STATISTICAL PHYSICS: EQUILIBRIUM STATISTICAL MECHANICS APPLIED
TO NONEQUILIBRIUM SYSTEMS
Statistical mechanics (statistical physics) is a quantitative
approach to the average behavior of a system containing many
particles, the approach derived from first principles and certain
simplifying assumptions concerning the nature and interactions of
the particles in the system. It is the most successful approach
to the behavior of physical systems containing many particles,
but its application has been limited to systems at or near
thermodynamic equilibrium.
... ... David A. Egolf (Los Alamos National Laboratory, US) now
reports on the application of statistical mechanics to systems
far from equilibrium, the author making the following points:
1) The author points out that statistical mechanics
describes the macroscopic physical properties of matter through a
probabilistic rather than a detailed knowledge of microscopic
dynamics, and that the theory has been applied successfully to a
wide variety of equilibrium systems, ranging from simple
molecular gases to *white dwarf stars. Statistical mechanics has
provided a theoretical understanding of the phases of matter, the
transitions between phases, and the deep property of universality
that unifies the descriptions of continuous transitions in
systems physically quite distinct (e.g., magnets and gases). In
nature, however, many systems are not in equilibrium, including,
for example, large-scale flows in the atmosphere, the evolution
of ecological systems, and the transport of energy in biological
cells. None of these situations can presently be understood with
equilibrium statistical mechanics.
2) Although the theory of equilibrium statistical mechanics
has been developed to extend it to systems only slightly
perturbed away from equilibrium (for which a quantitative
description of the evolution of the system is well-approximated
with only linear terms), in deterministic systems driven far from
equilibrium (where nonlinearities are important), theoretical
progress has been limited to relatively simple situations. In
particular, theorists have not yet developed an understanding of
the intriguing phenomenon of spatially extended *chaos, which is
typically characterized by disordered arrays of defects, patches
of uncorrelated regions, and a chaotic dynamics that persists
indefinitely. This remarkable behavior has been found in large,
deterministic, far-from-equilibrium systems as varied as
convecting horizontal fluid layers, chemical reaction-diffusion
systems, colonies of microorganisms, and *fibrillating heart
tissue. These disparate systems often display strikingly similar
macroscopic features and behaviors, which suggests the question
of whether one can construct a statistical predictive theory of
phases and transitions applicable to such chaotic far-from-
equilibrium systems.
3) The author reports that in his own computer-analysis
study, at intermediate coarse-grained scales, of a simple far-
from-equilibrium spatially extended chaotic model system, a
number of equilibrium properties, including *ergodicity and
*detailed balance, were found to be recovered by the system,
which indicates, the author suggests, that the macroscopic
behavior of some far-from-equilibrium systems might be understood
in terms of equilibrium statistical mechanics.
4) The essential idea resulting from this work and proposed
by the author is that simple far-from-equilibrium *dissipative
and extensively chaotic systems "can recover certain equilibrium
properties at coarse-grained scales with the underlying chaotic
dynamics serving as a temperature bath." The author concludes:
"The system studied here possesses some important differences
from true equilibrium systems. Perhaps the most intriguing is
that the effective noise strength (or temperature) is internally
generated and dependent on the state of the system, rather than
imposed by an external temperature bath. This difference poses a
challenge for explorations of the *second law of thermodynamics
in these systems."
-----------
David A. Egolf: Equilibrium regained: From nonequilibrium chaos
to statistical mechanics.
(Science 7 Jan 00 287:101)
QY: David A. Egolf: egolf@cnls.lanl.gov
-----------
Text Notes:
... ... *white dwarf stars: White dwarf stars are extremely dense
and compact stars that have undergone gravitational collapse.
Such stars, the final stage in the evolution of low-mass stars
after they have lost their outer layers, are approximately the
size of Earth, but with a mass approximately that of the Sun.
... ... *chaos: In this context, the term "chaos" refers to
unpredictable behavior arising in a system that obeys
deterministic laws but exhibits unpredictability. The essential
idea is that in certain systems small perturbations may produce a
cascade of larger perturbations, so that eventually the behavior
of such systems cannot be predicted from prior states no matter
if the systems appear simple and obey deterministic laws.
... ... *fibrillating heart tissue: Heart muscle fibrillation,
which is a dysfunction, is an extremely rapid desynchronized
contraction or twitching of individual muscle fibers in a muscle.
... ... *ergodicity: In general, ergodicity is a property of
dynamic systems containing a random variable (stochastic
systems): a system is said to be ergodic if it tends in
probability to a limiting form which is independent of the
initial conditions.
... ... *detailed balance: The principle of detailed balancing
(also called the principle of microscopic reversibility) states
that in equilibrium the probability (frequency) of the transition
of any microscopic part of a system from state A to state B
equals the probability (frequency) of the transition from state B
to state A.
... ... *dissipative: In general, a dissipative system
is a system that loses energy by conversion of energy into heat.
... ... *second law of thermodynamics: This law concerns the
direction that a natural process can take, and the law can be
stated in various ways, for example: a) heat cannot be
transferred from one body to a second body at a higher
temperature without producing some other effect; b) the entropy
of a closed system increases with time.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 7Apr00
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
PHYSICS: ON STATISTICAL PHYSICS AND ITS APPLICATIONS
Statistical physics (statistical mechanics) is the branch of
physics that attempts to explain the macroscopic properties of a
system on the basis of the properties of its microscopic
constituents. Usually the number of constituents is extremely
large, and all the characteristics of the constituents and their
interactions are presumed to be known. Although as a distinct
research area, statistical physics dates back to James Clerk
Maxwell (1831-1879) and Ludwig Boltzmann (1844-1906) and their
work on probability distributions in the kinetic theory of gases,
the field was substantially transformed in the 20th century, and
it has now been fruitfully applied to nearly all states of matter
including biological systems.
... ... Philip Ball (_Nature_, UK) presents a commentary on the
history and applications of statistical physics, the author
making the following points:
1) Statistical physics, and more specifically the theory of
transitions between states of matter, more or less defines what
we know about everyday matter and its transformations. In
addition, statistical physics provides a conceptual apparatus for
dealing with complex collective quantum phenomena of current
intense interest, particularly: a) Bose-Einstein condensation (in
which a collection of particles all occupy the same quantum
ground state); and b) high-temperature superconductivity (i.e.,
superconductivity above 35 degrees kelvin). Many of the states of
condensed matter that promise new technological applications,
ranging from *block copolymers to magnetic multilayers, can be
understood as the consequence of the kind of collective behavior
that statistical physics describes.
2) From the 1960s to the 1980s, statistical physicists were
primarily concerned with "critical points", the points in
thermodynamic phase diagrams at which two or more phases become
identical. The reasons for this interest are twofold: a) the
behavior of a system at its critical point also determines its
behavior in the broad vicinity of the critical point (within a
so-called "critical region"; b) the behavior of a system at a
critical point reveals kinships between different systems. For
example, liquid-gas criticality and the behavior of some magnets
at their Curie point (the temperature above which they lose their
*ferromagnetism) have numerically equal *critical exponents, and
both can be modeled by the so-called "*Ising model", a model
based on a lattice of two-state *spins. Commonality of critical
exponents gives rise to the idea of universality, the idea that
there are generic models in statistical physics that describe a
variety of apparently different many-body systems. This means
that solving one problem in statistical physics generally
delivers solutions for several other problems at the same time.
In addition, there is an implication that many-body behavior is
fundamentally determined only by global aspects such as the range
of interparticle forces, the dimensionality of the system, and
the nature of the "*order parameter" (whose abrupt change from a
zero to a non-zero value defines the transition from one state to
another).
3) A fruitful present area of research is the intersection
of statistical physics with quantum mechanics, in particular, the
many-body behavior of electrons in condensed matter. Correlated
behavior of electrons, in which electrons display a degree of
collective or coherent dynamics, produces superconductivity, the
*integer and fractional quantum Hall effect, so-called "*heavy-
fermion" behavior, *spin density waves, and *colossal
magnetoresistance. All of these collective phenomena have in
recent years been shown to underlie unexpected and potentially
useful properties of novel materials. Colossal magnetoresistance,
for example, may lead to the development of highly-sensitive
read-out heads for magnetic memories.
4) The author suggests that despite the proven value to cell
biology of some concepts from the study of phase transitions (for
example, the entropic effect of fluctuations on interactions of
lipid membranes), there remains much skepticism as to whether
biological phenomena can be approached as arising from collective
emergent behavior of statistical interacting ensembles rather
than from the closely controlled protein relays to which cell
biologists are accustomed. Yet statistical physics must
inevitably provide the baseline even in the cell: proteins may
phase-separate and membranes may adopt equilibrium conformations
unless actively opposed by cell processes.
-----------
Philip Ball: Transitions still to be made.
(Nature 2 Dec 99 402supp:C73)
QY: Philip Ball: p.ball@nature.com
-----------
Text Notes:
... ... *block copolymers: A copolymer in which a number of units
of the same monomer are located adjacent to one another (in
"blocks" of monomers).
... ... *ferromagnetism: A "ferromagnet" is a material (such as
iron) in which there may be a permanent *magnetic moment, and in
which the *spins of the atoms are aligned parallel to each other.
... ... *magnetic moments: (magnetic dipole moment) The intrinsic
spins of the electrons in an atom, together with the motion of
the electrons around the nucleus, give rise to a magnetic field
around the atom, and the magnitude of this field is related to
the magnetic dipole moment of the atom or ion.
... ... *critical exponents: In this context, a "critical
exponent" is a parameter that characterizes the temperature
dependence of a thermodynamic property of a substance near its
critical point. The temperature dependence has the form
|T-T(subc)|^(n), where T is the temperature, T(subc) is the
critical temperature, and (n) is the critical exponent.
... ... *Ising model: In general, a simplified model in which the
atomic *spins are assumed to be aligned parallel or antiparallel
in a given direction.
... ... *spins: In quantum mechanics, electrons, protons, and
neutrons have an intrinsic angular momentum known as "spin", and
a magnetic moment parallel or antiparallel to that angular
momentum. When electrons are combined together to form an atom or
ion, there is a resultant angular momentum which is a combination
of the intrinsic spin of the electrons and the angular momentum
due to their motion about the nucleus, and this is the "spin" of
the atom or ion. Atoms or ions with non-zero spin are magnetic
atoms or ions. The idea of electron spin was first proposed by
Goudsmit and Uhlenbeck in 1925 to explain the splitting of atomic
spectroscopic emission lines in the presence of a magnetic field.
Elementary particle spin involves a virtual rotation about the
axis of the particle, which means only two spin states are
possible, one clockwise and one counterclockwise.
... ... *order parameter: In general, a quantity that
characterizes the phase of a system below its transition
temperature, the parameter having a nonzero value below the
transition temperature and a zero value above the transition
temperature. If the phase transition is continuous, the order
parameter falls to zero continuously as the transition
temperature is approached.
... ... *integer and fractional quantum Hall effect: In classical
physics, the Hall effect is the development of a transverse
voltage across a current-carrying conductor in a magnetic field,
the voltage being perpendicular to both the direction of the
current and the direction of the magnetic field. In quantum
physics, there are two other Hall effects, an integer charge
quantum Hall effect, and a fractional charge quantum Hall effect,
these quantum Hall effects being observed at extremely low
temperatures (a few degrees Kelvin) and extremely intense
magnetic fields (at least several tesla). Both quantum Hall
effects were first noted in the 1980s, and the fractional quantum
Hall effect, although experimentally observed, has not been
theoretically resolved.
... ... *heavy-fermion: "Heavy-fermion systems" are solids in
which electrons behave as if they have masses several hundred
times their normal masses. Substances containing such electrons
have unusual thermodynamic, magnetic, and superconducting
properties that are not completely understood.
... ... *spin density waves: In general, propagating collective
spin-variation excitations associated with certain magnetic
systems.
... ... *colossal magnetoresistance: (giant magnetoresistance)
The term "magnetoresistance" refers to a change in the electrical
resistance of a conductor or semiconductor upon the application
of a magnetic field, a property of certain systems. Giant
magnetoresistance is a quantum mechanical effect observed in
magnetic thin-film structures composed of alternating
ferromagnetic and nonmagnetic layers.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 3Mar00
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
ON SINGLE MOLECULE PHYSICS AND CHEMISTRY
Only a few decades ago, most scientists believed that individual
molecules would not come within the domain of experimental
observations within their lifetime, if ever, and that the
statistical ensemble properties of molecules were therefore the
only properties of relevance. That view has now undergone a
dramatic alteration as a consequence of technological advances,
and there is much excitement evident in many laboratories over
the prospects of single-molecule explorations in physics,
chemistry, and biology.
... ... C. Bai et al (4 authors at 3 installations, CN US)
present a short review of recent work in single-molecule physics
and chemistry, the authors making the following points:
1) The authors point out that when Richard Feynman (1918-
1988) was bothered while looking through one of the first
*scanning tunneling microscopes, he was upset to have been
interrupted because seeing the images of singe atoms was a
"religious experience". For many generations of scientists, the
molecule was both the concrete ultimate entity upon which our
understanding of the everyday world was based, and at the same
time an elusive intellectual construct whose very existence could
only be inferred circumstantially by experiments on macroscopic
samples. Thus, seeing an individual atom or molecule in motion
brings immediate emotional impact to this central concept of
modern thought.
2) The authors ask: "When is molecular individuality
important?" The new possibility of studying single molecules is
important because molecular individuality does finally come into
play when the molecule is a complex entity. This may occur
because the molecule itself may have an intricate internal
structure -- e.g., a biomolecule -- resulting in a complex energy
landscape. Alternatively, the molecule may be part of a complex
environment that substantially changes the behavior of the
molecule. Here, distinguishing different molecules at different
locales is crucial for understanding the system as a whole.
Biomolecules in living cells are examples of this. Even simple
inorganic molecules on structured surfaces or in disordered
systems such as viscous liquids or glasses provide situations in
which molecular individuality matters. In all of these cases, the
capability of studying an individual molecule over time can
provide new insights unavailable by straightforward experiments
on macroscopic populations of molecules.
3) With the aid of *scanning probe microscopy, direct
observations of entire arrays of atoms, molecules, and the fine
structures of molecular aggregates have become possible. The
ability to precisely control probes permits the study of long-
range structures made by molecules lying on surfaces. However,
although pretty pictures of such systems are easy to construct,
obtaining quantitative characteristics of surface-bound molecules
is not entirely straightforward, and the rigorous interpretation
of scanning probe microscopy images requires substantial
theoretical as well as experimental effort.
4) The authors conclude: "We are only at the beginning, but
it is clear there is much to be discovered of a fundamental
nature about complex molecules viewed as individuals. Perhaps
equally important will be the idea of single molecule control.
Now that experiments interact with molecules at an individual
level, we can try to control them as individuals, not as
populations. A molecule under active control by an adaptive
environment will be a new beast. Such tamed molecules may well
resemble much more the elegant engineered machinery of everyday
experience than the unruly, wild molecules we are used to
studying today."
-----------
C. Bai et al: Single molecule physics and chemistry.
(Proc. Natl. Acad. Sci. US 28 Sep 99 96:11075)
QY: Chunli Bai, Institute of Chemistry, The Chinese Academy of
Sciences, Beijing 100080 CN.
-----------
Text Notes:
... ... *scanning tunneling microscopes: See previous report(s).
... ... *scanning probe microscopy: See previous report(s).
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 5Dec99
For more information: http://scienceweek.com/swfr.htm
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
5. PLANETARY SCIENCE: ON THE MOON GANYMEDE
One of the major propositions of Ptolemaic astronomy (named
after Claudius Ptolemaeus [c.100-c.170], who probably found most
of his ideas in Hipparchus [170 BC-120 BC]) was the uniqueness of
the Earth-Moon system. Ptolemaic astronomy, which endured
approximately 1500 years, was refuted by Nicolaus Copernicus
(1473-1543), and then later by Galileo Galilei (1564-1642) and
other early astronomers. It was during the month of January in
the year 1610 that the idea of the uniqueness of the Earth-Moon
system was proved wrong by the discovery by Galileo of four moons
of Jupiter with a 32-power telescope of his own design and
manufacture. Galileo proposed that the satellites be named the
Medicean stars, in honor of his patron, Cosimo II de' Medici, but
the moons came to be known as the "Galilean satellites", in honor
of their discoverer.
Jupiter has 16 known moons, and the Galilean satellites are
the largest. In order of increasing distance from Jupiter, the
Galilean satellites are Io, Europa, Ganymede, and Callisto. Roman
numerals are assigned to the satellites in order of their
discovery, with Ganymede also known as "Jupiter III".
With a diameter of 5262 kilometers, Ganymede is not only the
largest moon of Jupiter, but also the largest moon in the Solar
System -- in fact, Ganymede is larger than the planet Mercury.
Ganymede orbits Jupiter at a distance of approximately 1 million
kilometers, and it has a relatively low density of 1.93 grams per
cubic centimeter, which suggests a composition approximately half
rock and half ice by mass.
Ganymede was observed at close range in 1979 by the US
Voyager 1 and 2 planetary probes, and by the Galileo spacecraft
in the late 1990s. It has two principal types of terrain, one
dark and one bright. The dark terrain is present in broad regions
separated by bands of bright terrain. Both terrains have impact
craters, but the density of craters is higher in the dark
terrain, which suggests that the dark terrain is the older
terrain. On Ganymede, craters of a given diameter are generally
much shallower than craters of the same diameter on rocky bodies,
which suggests the involvement of cold viscous flow of the ice-
rich crust. Many of the craters have rays consisting of very
bright ice deposits. Much of the bright terrain of Ganymede is
covered by complex patterns of long and narrow topographic
grooves typically several hundred meters deep and as much as
hundreds of kilometers long. These grooves often lie in parallel
sets, with adjacent grooves spaced approximately 5 to 10
kilometers apart. It is believed that the bright terrain in the
grooves may have been formed during a period of tectonic activity
in which internally generated stresses disrupted and fractured
the crust. The exact time at which this activity occurred is
unknown, but the density of craters in the bright terrain
suggests it happened early in Ganymede's history.
In this context, the term "embayment" refers to the
deformation of a shoreline into a bay contour by an advancing
liquid. In this context, the term "rift" refers in general to a
split between two bodies that were once joined.
... ... P.M. Schenk et al (4 authors at 4 installations, US)
present an analysis of the terrain of Ganymede, the authors
making the following points:
1) The authors report digital elevation models of parts of
the surface of Ganymede, the models derived from stereo pairs
combining data from the Voyager and Galileo spacecraft, which
reveal bright and smooth terrains that lie at roughly constant
elevations 100 to 1000 meters below the surrounding rougher
terrains. These topographic data, together with new images that
show fine-scale embayment and burial of older features, indicate
that the smooth terrains were formed by flooding of shallow
structural troughs by low-viscosity water-ice lavas.
2) The authors report that the oldest and most deformed
areas (the "reticulate" terrains) in general have the highest
relative elevations, whereas units of the most common resurfaced
type -- the grooved terrain -- lie at elevations between those of
the smooth and reticulate terrains. The authors suggest that
bright terrain, which accounts for some two-thirds of the
surface, probably results from a continuum of processes,
including crustal rifting, shallow flooding, and groove
formation. Volcanism plays an integral role in these processes
and is consistent with partial melting of the interior of
Ganymede.
-----------
P.M. Schenk et al: Flooding of Ganymede's bright terrains by low-
viscosity water-ice lavas.
(Nature 1 Mar 01 410:57)
QY: Paul M. Schenk: schenk@lpi.usra.edu
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 18May01
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
SURFACE CHEMICALS OF JUPITER'S MOONS CALLISTO AND GANYMEDE
... Callisto is the second largest of Jupiter's moons, diameter
4800 kilometers, and evidence indicates it contains a relatively
large proportion of water-ice. One way of examining the surface
of a moon or planet is by means of its reflectance spectra at
various wave- lengths, particularly near-infrared wavelengths,
and these spectra make possible chemical analysis of the surface.
T. B. McCord et al (12 authors at 4 installations, US) report
that an analysis of reflectance spectra returned by the Galileo
mission near-infrared mapping spectrometer indicates the presence
of the following in surface materials of Callisto and Ganymede:
carbon dioxide, organic materials such as tholins, and compounds
containing an SH-functional group, with water ice and hydrated
minerals the primary surface constituents. The authors suggest
that the organic molecules, and perhaps the other molecules
detected, may accumulate on the surfaces of the Galilean moons
from outside the Jupiter system.
QY: T. B. McCord
(Science 10 Oct 1997) (Science-Week 31 Oct 97)
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
EVIDENCE FOR THE PRESENCE OF OXYGEN ON JUPITER'S MOON GANYMEDE
Optical reflectance measurements during the past two years of
Jupiter's moon Ganymede have revealed the presence of oxygen. The
spectra, however, indicate a complicated system. This week, R. A.
Vidal et al (University of Virginia, US; Teikyo University, JP)
reported laboratory studies to determine whether similar optical
reflectance spectra could result from condensed oxygen embedded
in ice or other materials that may be present on Ganymede's
surface. The laboratory system was cooled to 26 degrees Kelvin,
and at that temperature it was indeed found that the spectra are
very similar. The authors suggest that the absorption bands in
Ganymede's spectrum were not produced in the relatively warm
surface of the satellite, but in a much colder source, and that
solid O(2) may exist in a cold subsurface layer or in an
atmospheric haze. (Science 20 Jun 97) (Science-Week 26 Jun 97)
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
MAGNETIC FIELDS OF JUPITER'S MOONS INTEREST EXOBIOLOGISTS
The Earth's intrinsic magnetic field is due to its electrically
conducting liquid metal core, the liquidity maintained by high
internal temperatures. It is thus considered that any other
planetary body with an intrinsic magnetic field will also have
an electrically conducting metal core at high temperatures, and
therefore have a heated interior no matter what the surface
temperature. G. R. Sarson et al (University of Exeter, UK; and
University of California at Los Angeles, US) have now provided
simulation evidence using the equations of magnetohydrodynamics
and data from the Galileo orbiter that Ganymede is operating as
a magnetic dynamo in its own right, while Io, in the presence of
Jupiter's magnetic field, also possesses an intrinsic magnetic
dynamo. Apart from general astronomical interest, the results
are of interest to exobiologists because they suggest these two
moons of Jupiter might harbor some life form in their relatively
warm interiors. (Science 16 May 97) (Science-Week 22 May 97)
For more information: http://scienceweek.com/swfr.htm
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
6. HISTORY OF SCIENCE: ON LANGUAGE REFORM IN CHEMISTRY
An argument can be made that nomenclature in science is as
important as data, since nomenclature represents the prevailing
conceptual organization of observations. Certainly, researchers
in most sciences are constrained to adhere to the nomenclature
rules of their field. Molecular biology is currently in a phase
of general nomenclature chaos with respect to the naming of
genes, but hopefully that phase will soon pass. Meanwhile,
nomenclatures in other areas of biology are more organized, and
18th century plant taxonomy, in fact, served as a model for the
nomenclature revolution in chemistry that occurred in conjunction
with the "new chemistry" proposed by Antoine Lavoisier (1743-
1794).
Lavoisier is often cited as the instigator of chemical
nomenclature reform at the end of the 18th century, but four
chemists were the prime movers of this reform: Lavoisier, Louis
Guyton de Morveau (1737-1816), Claude Berthollet (1748-1822),
Antoine Fourcroy (1755-1809). Of the four, Guyton de Morveau,
probably deserves more credit than the others, his efforts
culminating in the publication of his _Method of Chemical
Nomenclature_ in 1787 [*Note #1]. All the above chemists,
however, collaborated in the nomenclature revision program, which
quickly became accepted after the publication of Lavoisier's
influential textbook _Elementary Treatise on Chemistry_ in 1789
[*Note #2]. Perhaps the most important general nomenclature
revision was the adoption of a binomial scheme for naming
compounds (influenced by the scheme then current in botany), but
of specific importance was the renaming of "*dephlogisticated
air" ("empyreal air; vital air) as "oxygen", and the renaming of
"inflammable air" as "hydrogen", both new names based on
prevailing knowledge of chemistry rather than on ambiguous
attributes.
... ... Bernadette Bensaude-Vincent (University of Paris, FR)
presents a commentary on language reform in chemistry, the author
making the following points:
1) Guyton de Morveau initiated the French 18th century
chemical nomenclature reform project and established a set of
basic principles: a) nomenclature should reveal "the nature of
things"; b) simple substances should have simple names evoking
their most characteristic property; c) compound names should
express the composition of chemical compounds; d) Greek
etymologies should be used in preference to Latin.
2) Guyton de Morveau began his attempt to reform chemical
nomenclature in 1782 and submitted his project to the Paris
Academy of Sciences in January 1787. At the Academy, Guyton
encountered a fierce debate concerning the existence of
"phlogiston", the principle that was believed to explain
combustion and reduction. Although most chemists at that time
believed in phlogiston, Lavoisier's explanation of combustion was
quite different. Guyton allied himself with Lavoisier, and with
the help of Lavoisier, Berthollet, and Fourcroy, Guyton published
a revised project in the spring of 1787, the revision making no
mention of "phlogiston", but instead containing new words such as
"oxygen", from Greek words meaning "acidifying principle", the
new term stemming from Lavoisier's idea that all acids contained
oxygen.
3) The author points out that the language reform of 1787-
1789 was an integral part of the formation of the autonomous
discipline of chemistry, contributed to the subordination of
pharmacy to chemistry, and contributed to the redefinition of the
chemical arts as applied chemistry. The new language forged by
academic chemists separated many users of chemical substances
from their own traditions. The new language ignored the
physiological senses of chemists, banished all reference to
geographical origins or the discovery of the substances, and
imposed an analytical quantitative logic on chemical
nomenclature. Although the use of this logic proved to be a
valuable method over time, the principles of the system were
never strictly applied. Oxygen, for example, should have been
renamed when Humphrey Davy (1778-1829) established that many
acids do not contain oxygen. Colors and odors were restored after
the discovery of chlorine and iodine, named from the Greek for
"yellowish-green" and "violet", respectively. Bromine was named
from the Greek word for "stink". Morphine was named after
Morpheus, the god of dreams. Benzene was named after Styrax
benzoin, a tree native to Sumatra and Java. Scandium, germanium,
and polonium were named after political entities, and in the 20th
century various new elements were named after historical
scientific figures. In general, the systematization imposed by
the four 18th century reformer chemists in the name of
rationality remained an ideal often contradicted by practice. At
present, nomenclature rules in chemistry are under the control of
a permanent commission, the International Union of Pure and
Applied Chemistry (IUPAC).
-----------
Bernadette Bensaude-Vincent: Chemical analysis.
(Nature 22 Mar 01 410:415)
QY: Bernadette Bensaude-Vincent, University of Paris X. 200
Avenue de la Republique, 92001 Nanterre Cedex, FR.
-----------
Text Notes:
... ... *Note #1: Louis Bernard Guyton de Morveau (1737-1816) was
an interesting personage. His first profession was that of an
attorney. In 1776, while still an attorney, he published the
_Elements of Theoretical and Practical Chemistry_, a major
attempt to quantify chemical affinities. In 1782, he gave up the
law and devoted himself full-time to chemistry. In 1795, he
founded the Ecole Polytechnique and taught there until 1805.
Guyton was one of the first to conclude that iron and steel
differ solely in their carbon content. He made improvements in
the manufacture of gunpowder. He was the first to use chlorine
and hydrochloric acid gas as disinfectants. He was one of the
first balloonists, making two flights in 1784 and helping in the
organization of the world's first air force, the Compagnie
d'Aerostiers, whose reconnaissance balloonists assisted the
French army in several battles during the Napoleonic wars.
... ... *Note #2: Concerning nomenclature in chemistry, the
following passage appears in Lavoisier's _A General Introduction
to Chemistry_ (1789):
"It is impossible to dissociate language from science or
science from language, because every natural science always
involves three things: the sequence of phenomena on which the
science is based; the abstract concepts which call these
phenomena to mind; and the words in which the concepts are
expressed. To call forth a concept, a word is needed; to portray
a phenomenon, a concept is needed. All three mirror one and same
reality. Words are thus required to preserve and transmit ideas,
so that it is clear that the advancement of a science and the
improvement of its technical vocabulary go hand in hand. No
matter how certain we are of the phenomena, no matter how
adequately our concepts reflect them, we cannot help perpetuating
wrong ideas unless we have a precise terminology in which to
express ourselves."
Lavoisier, considered the father of modern chemistry, was no
doubt the most eminent scientist to ever suffer death by the
guillotine. In 1780, as a member of the French Academy of
Sciences, Lavoisier was active in rejecting the application to
the Academy of a certain physician Jean-Paul Marat (1743-1793).
Marat apparently did not forget. During the French Revolution
(1787-1799), Marat became a powerful revolutionary leader, and
Marat was instrumental in bringing Lavoisier to trial for his
investments in a much-hated company that collected taxes for the
French government. Lavoisier was guillotined May 8, 1794 and
buried in an unmarked grave. (Marat did not live to see this:
Marat himself was assassinated in July 1793.)
... ... *dephlogisticated air: In this context, the term
"phlogiston" refers to a 17th and 18th century chemical theory
involving a hypothetical principle of fire. The idea was that
every combustible substance is in part composed of phlogiston,
with the phenomenon of burning caused by the liberation of
phlogiston and the "dephlogistonated" substance remaining as ash
or residue. The phlogiston theory was experimentally discredited
by Lavoisier beginning in 1770, who showed that the newly
discovered element oxygen was always involved in combustion.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 18May01
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
ON LINGUISTIC CHAOS IN MOLECULAR BIOLOGY
Nomenclature anarchy in molecular biology is apparently once
again the focus of attention, although no remedies are evident.
In a recent article, Paul Smaglik writes, "Gene and protein names
often are based on the flamboyant, the descriptive, and the
intentionally obscure. For many researchers, naming their
discovery may be a rare opportunity to imbue their science with
creativity." But Lawrence Puente (University of Alberta, CA)
points out that creativity plus competition can equal confusion.
Julia A. White (University College London, UK), a member of the
Nomenclature Committee of the Human Genome Organization, says
that although the committee strives to sort out linguistic chaos,
the committee remains behind as a result of the speed and scope
of the Human Genome Project. With hundreds of thousands of genes
and proteins still to be named, molecular biology is in dire need
of nomenclature regulation.
(The Scientist 30 Mar 98) (Science-Week 17 Apr 98)
-------------------
Related Background:
MORE DISCUSSION OF ACRONYM ANARCHY IN MOLECULAR BIOLOGY
There are approximately 100,000 genes in the human genome, and
approximately 100,000 expressed proteins, the total certainly
enough to require a dictionary of names. Add to this total the
total of acronyms used to identify cell-lines, cell receptors,
metabolic pathways, carbohydrates, etc., and the dictionary would
require a second volume. In the early days of biochemistry and
molecular biology, when few genes and their expressed proteins
had been identified, everyone could more or less remember the
names of the macromolecular entities being studied by the people
in the laboratory down the hall. These days that is unlikely, and
made more unlikely by the tendency of many molecular biologists
to choose ad hoc names that are often more cute than technically
pertinent, and to obfuscate their research papers with acronyms
by the dozen in a single paper. We know of at least one instance
where an acronym for a cell-line in a paper from a group at the
US National Institutes of Health was not defined anywhere in the
paper, where telephone calls to molecular biologists produced no
one who knew what cell-line was involved, and where a query to
the authors of the paper did not produce a response for nearly
three weeks. As one scientist recently put it: "If you make your
paper difficult to read, at least no one can call you stupid." A
recent exchange of letters in the journal Nature revisits this
recurrent problem of nomenclature in molecular biology. It seems
there are indeed existing committees concerned with regulating
the nomenclature of molecular biology, but it also seems no one
pays any attention to them. Puente et al (Univ. of Alberta, CA)
refer to the present situation as "acronym anarchy". We agree. We
would add that if the in-house editors of the leading general
journals such as Science and Nature would refuse to publish these
unduly obfuscated papers, they would be doing a service to the
scientific community.
QY: L. Puente (Nature 27 Nov 97)
-------------------
Related Background:
A CRITICISM OF NOMENCLATURE IN MOLECULAR BIOLOGY
Nomenclature is a serious problem in all the sciences, since as
new discoveries are made, new entities identified, new concepts
formulated, new names for these things must be found so that
scientists can communicate with each other with some degree of
precision. Most sciences have nomenclature committees that meet
regularly to standardize current terminology and make decisions
about new terminology. Molecular biology, one of the most active
scientific disciplines these days, has no such constraints, and
apparently there is growing concern that the arbitrary and some-
times whimsical naming of new entities ("miranda", "prospero",
"numb", "inscrutable") in molecular biology, with the same entity
often sporting a number of names, has reached the stage of
promoting confusion and the inability of scientists to deal
efficiently with the literature. In a recent editorial
criticizing nomenclature practices in molecular biology, the journal
Nature says, "Regrettably, molecular biologists have followed the
particle physicists' whimsy with obscurantist enthusiasm." In
particle physics, of course, we already have "quark",
"strangeness", "charm", "color", "top", "bottom", etc., which the
editorial calls a "descent into whimsy" started by Murray
Gell-Mann in the 1960s, who evidently took the term "quark" from
a phrase in James Joyce's FINNEGAN'S WAKE. What is interesting is
that the same journal which is criticizing whimsical scientific
nomenclature is apparently quite fond of headlines involving
whimsical wordplay, puns, and metaphors when describing
scientific research results. If a consequence of this attention
to nomenclature will be a more rational use of language in
science, many people will no doubt be appreciative of it.
(Nature 4 Sep 97)
-------------------
Related Background:
PHYSICISTS ORGANIZE AGAINST IMPENETRABLE JARGON IN PHYSICS
A group of working physicists and journal editors, under the
leadership of Mitio Inokuti (Argonne National Laboratory, US) and
Ugo Fano (University of Chicago, US) has come into existence with
the objective of reforming the publication standards for papers
in physics. The problem is that physicists no longer understand
each other, their communication warped by "unexplained acronyms,
cryptic symbols, endless sentences, and monstrous graphs".
Analyzing the psychology of why this exists, Phillip Schewe
(American Institute of Physics, US) says, "You lose all your
readers, but at least you can't be accused of being an idiot.
Instead, the readers are made to feel like they're idiots." The
problem, of course, is just as severe in chemistry and biology.
(Science 15 Aug 97)
For more information: http://scienceweek.com/swfr.htm
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
7. IN FOCUS: ON PLANCK, BOLTZMANN, AND ENTROPY
"If there is a single concept that unifies the long and fruitful
scientific career of Max Planck, it is the concept of entropy.
From the Munich dissertation which he wrote at the age of 21,
right through to the papers he wrote during his late seventies,
the Second Law of Thermodynamics and the associated idea of
entropy were always central in his thought. Although much of his
work can be viewed as an extended series of variations on what he
called his pet theme ("Lieblingsthema"), the theme itself was
radically altered in 1900. In that year Planck introduced, in his
theory of the black-body radiation spectrum, the idea which
immortalized his name, the idea of energy quanta. This idea grew
directly from Planck's years of study of the way in which the
second law of thermodynamics applied to the behavior of
radiation. But despite its connections with his work on entropy
during the previous 20 years, it was the very success of his
theory of radiation that forced Planck to make a thorough
revision of his ideas on entropy. Before 1900, Planck had
resolutely followed the single line of pure thermodynamics in his
work, avoiding the difficulties that surrounded the path of
kinetic theory. He was willing to grant that the attempts to
expose the molecular basis of macroscopic behavior offered the
hope of more fundamental insight into nature; but he expressed
his doubts, on more than one occasion, that these attempts to dig
deeper than the laws of thermodynamics could meet with real
success in the foreseeable future. At no point in any of the 40
or so papers that he wrote prior to 1900 did Planck use, or even
refer to, the relationship that Ludwig Boltzmann had discovered
between entropy and the probability of molecular configurations.
The muse of entropy was as dear to Boltzmann's heart as to
Planck's, but how different she appeared to her two admirers!"
-----------
Martin J. Klein: Planck, Entropy, and Quanta, 1901-1906.
(The Natural Philosopher 1963 1:83)
-------------------
SCIENCE-WEEK http://scienceweek.com 18May01
For more information: http://scienceweek.com/swfr.htm
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