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.

August 4, 2000 -- Vol. 4 Number 31

-----------------------------------------------

I am somehow less interested in the weight and
convolutions of Einstein's brain than in the near
certainty that people of equal talent have lived
and died in cotton fields and sweatshops.
-- Stephen Jay Gould

-----------------------------------------------

Contents of this Issue:

1. Science Policy:
Is US Health Care Really the Best in the World?
-----------------------------------------------
Harmful effects of health care interventions may account for a
substantial proportion of the excess deaths in the US compared
with other comparably industrialized nations.
(Includes related background material.)

2. Neurobiology:
Induction of Neurogenesis in the Mammalian Brain
------------------------------------------------
New experiments provide further evidence that endogenous neural
precursors can be induced to differentiate into mature neurons in
regions of adult mammalian neocortex that do not normally undergo
any neurogenesis.
(Includes related background material.)

3. Biochemistry:
An RNA Enzyme (Ribozyme) with Two Possible Folds and Two Actions
----------------------------------------------------------------
New experiments demonstrate that a single RNA nucleotide sequence
that can assume either one of two ribozyme folds and catalyze two
respective reactions (a ligation reaction and a cleavage
reaction).
(Includes related background material.)

4. Chemistry:
Synthetic Receptors and Alkali-Metal-Pi Binding in Proteins
-----------------------------------------------------------
A model chemical system provides experimental evidence supporting
the idea that in biological systems aromatic amino acids can bind
cations.

5. Materials Science:
On The Smallest Random Laser
----------------------------
A new inexpensive ultra-small (1.7 microns) random laser may be
the beginning of a new technology in optical devices.
(Includes related background material.)

6. Experimental Physics:
On Exceeding the Velocity of Light
----------------------------------
The transmission of certain light pulses over short distances
with apparent velocities greater than the speed of light in a
vacuum does not violate either the theory of special relativity
or the principle of causality.

7. Focus Report:
On the Oldest Life on Earth

8. From the SW Archive:
On the Physicist Maria Goeppert-Mayer

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

1. SCIENCE POLICY:
IS US HEALTH CARE REALLY THE BEST IN THE WORLD?
In general, the health of a population is "public health", and
public health is for the most part a consequence of both culture
and national policy. The US is one of the major developed
countries on the planet, with what is probably the most developed
scientific enterprise, but is this intense scientific effort
correlated with a comparable high level of health care for the US
population? For the most part, the answer is apparently no.
... ... Barbara Starfield (Johns Hopkins University, US) presents
a commentary on current assessments of US health care, the author
making the following points:
     Information concerning deficiencies of US medical care has
been accumulating, although the high cost of the US health care
is apparently tolerated under the assumption that better health
results from more expensive care. The facts are as follows:
     1) More than 40 million people in the US have no health
insurance.
     2) 20% to 30% of patients in the US receive contraindicated
care.
     3) An estimated 44,000 to 98,000 people in the US die each
year as a result of medical errors.
     4) According to several studies, the US population does not
have anywhere near the best health in the world. Of 13 countries
in a recent comparison, the US ranks an average of 12th (second
from the bottom) for 16 available health indicators. Countries in
order of average ranking on the health indicators (with first as
best) are Japan, Sweden, Canada, France, Australia, Spain,
Finland, the Netherlands, the UK, Denmark, Belgium, the US, and
Germany. On separate indicators, the rankings of the US are as
follows:
... ... Low birth-weight percentages: 13th (last in ranking)
... ... Neonatal mortality and infant mortality overall: 13th
... ... Postneonatal mortality: 11th
... ... Life expectancy at 1 year for females: 11th
... ... Life expectancy at 1 year for males: 12th
... ... Life expectancy at 15 years: females 10th; males 12th
... ... Life expectancy at 40 years: females 10th; males 9th
... ... Life expectancy at 65 years: females 7th; males 7th
... ... Life expectancy at 80 years: females 3rd; males 3rd
... ... Age-adjusted mortality: 10th
     5) The poor performance of the US was recently confirmed by
the World Health Organization, which used different indicators,
the WHO report ranking the US as 15th among 25 industrialized
countries. Although common explanations for the poor performance
of the US in these rankings blame the "bad behavior" of Americans
(e.g., smoking, drinking, violence, etc.), the data comparing
such behavior to the behavior of the people in other countries
indicates otherwise. Concerning the long-existing poor ranking of
the US with regard to infant mortality, this low-ranking is not
the result of the high percentages of low birth-weight and infant
mortality among the US black population, since the international
ranking hardly changes when data for the white population only
are used.
     6) The US health care system may contribute to poor health
through its adverse effects. For example, US estimates of the
combined effect of errors and adverse effects that occur because
of *iatrogenic damage include:
... ... 12,000 deaths per year from unnecessary surgery.
... ... 7000 deaths per year from medication errors in hospitals.
... ... 20,000 deaths per year from other errors in hospitals.
... ... 80,000 deaths per year from *nosocomial infections in
hospitals.
... ... 106,000 deaths per year from non-error adverse effects of
medications.
     These total to 225,000 deaths per year from iatrogenic
causes, so that iatrogenic cause is the 3rd leading cause of
death in the US, after deaths from heart disease and cancer.
     7) The author concludes: "Recognition of the harmful effects
of health care interventions, and the likely possibility that
they account for a substantial proportion of the excess deaths in
the US compared with other comparably industrialized nations,
sheds new light on imperatives for research and health policy.
Alternative explanations for these realities deserve intensive
exploration."
-----------
Barbara Starfield: Is US health really the best in the world?
(J. Amer. Med. Assoc. 26 Jul 00 284:483)
QY: Barbara Starfield [bstarfie@jhsph.edu]
-----------
Text Notes:
... ... *iatrogenic: In general, this denotes any result produced
by surgery or other treatment. In this context, and in the usual
usage, the term is used for a result that is unwanted and
injurious to the patient (e.g., an infection due to contaminated
surgical instruments).
... ... *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 the bacterial pathogen
Staphylococcus aureus on the skin of their hands, and that 60 to
70 percent of all hospital workers carry S. aureus in their
nostrils.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 4Aug00
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
SCIENCE POLICY:
ON PUBLIC HEALTH DISPARITIES
Public health is best distinguished from clinical medicine by its
emphasis on preventing disease rather than curing it, and by the
focus of public health on populations and communities rather than
on the individual patient.
... ... Barry R. Bloom (Harvard School of Public Health, US)
presents a commentary on recent and current public health with a
focus on disparities both globally and in the US. The author
makes the following points:
     1) Half of all the increases in life expectancy in recorded
history occurred within the 20th century, and most increases
occurred within the first half of the 20th century and before the
introduction of modern drugs and vaccines. The major gains in
health in the past century are attributable largely to the impact
of public health and disease prevention, rather than to medical
interventions.
     2) In the past 20 years, deaths from heart attacks and
strokes in the US have dropped by 30 to 50 percent, in part as a
result of behavior changes, in part as a result of primary
prevention with medications. Smoking, estimated to be responsible
for approximately 20 percent of all deaths in the US, has
declined from 42 percent to 25 percent in adults over 30 years of
age (although it has increased to 36 percent among US teenagers
and is still rising). In addition, the use of the drug tamoxifen
has reduced the incidence of breast cancer by 45 percent in women
at high risk.
     3) Perhaps the most dramatic effect of all is the impact of
immunization. Vaccines have eliminated smallpox from the world
and polio from the Northern Hemisphere, and have reduced the
incidence of measles, rubella, tetanus, diphtheria, and
meningitis in many countries to a handful of cases each year,
saving millions of lives and billions of dollars. Vaccines remain
the most cost-effective intervention known for preventing death
and disease. In 1999, for the first time, infectious diseases
were no longer the largest cause of death worldwide.
     4) Unfortunately, the benefits of biomedical science and
public health are not uniformly distributed, and the disparities
are striking. Japan, with the highest life expectancy of 80
years, contrasts with Sierra Leone and its life expectancy of 37
years in 1998. What is most striking are the strong disparities
within single countries. It is generally believed that in
industrialized countries life expectancy is high for everyone and
that the major health issues center on the quality of life and
health care rather than on life expectancy. But the
contradictions to this idea are striking:
... ... a) People born in particular rural counties of Minnesota,
Colorado, Iowa, or Wisconsin on average will live 25 years longer
than those born in 4 counties of South Dakota, 23 years longer
than in 12 counties in Mississippi and Alabama, and 22 years
longer than people born in Washington, DC or Baltimore, MD.
... ... b) The variance in life expectancy in the US between
women of Japanese extraction in Bergen County, New Jersey, and
Bennett County, South Dakota is 41 years.
... ... c) Overall, disparities in life expectancy between
different parts of the US are greater than for any other nation
in the world, and the reasons for this are not clear. As in many
countries, the correlation in the US between per capita income
and life expectancy is not particularly good. For example, per
capita income is significantly higher in the county of
Washington, DC than in several counties along the Texas-Mexican
border, but life expectancy is significantly lower -- by
approximately 15 years -- in Washington, DC.
     5) The author concludes: "We know that cardiovascular
disease, psychiatric disease, and physical injuries represent the
major global burdens of disease and disability in industrialized
and developing countries alike. The challenge for biomedical
science and public health in the coming century is to develop the
population-based interventions needed to reduce these burdens."
-----------
Barry R. Bloom: The future of public health.
(Nature 2 Dec 99 402supp:C63)
QY: Barry R. Bloom [bbloom@hsph.harvard.edu]
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 10Mar00
For more information: http://scienceweek.com/swfr.htm

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

2. NEUROBIOLOGY:
INDUCTION OF NEUROGENESIS IN THE MAMMALIAN BRAIN
During most of the 20th century, a dogma that pervaded all
teaching and textbooks in neurobiology was that neurons in the
adult mammalian central nervous system (including the adult human
central nervous system) are not replaced after destruction. No
regeneration, no neurogenesis, no repair of damaged central
nervous system tissue. These days we know better; there are
exceptions and the dogma is false. We have evidence of
neurogenesis in limited but important areas of the adult
mammalian brain: the *hippocampus, the *olfactory bulb, and some
regions of the *cerebral cortex of one species of monkey
(Macaque). The continuing refutation of the dogma is based
largely on new techniques for marking the appearance of new
neurons, and many neurobiologists are now hopeful that methods
will eventually be found to induce neurogenesis useful to
clinical neurology.
... ... S.S. Magavi et al (3 authors at Harvard University, US)
now provide evidence that endogenous neural precursors (*stem
cells) can be induced in situ to differentiate into mature
neurons in regions of adult mammalian neocortex that do not
normally undergo any neurogenesis. The authors report the
following:
     1) The apparent stem cell differentiation into mature
neurons occurs in a layer- and region-specific manner, and the
new neurons can apparently reconstruct appropriate *cortico-
thalamic connections.
     2) In their experiments, the authors induced synchronous
*apoptotic degeneration of corticothalamic neurons in layer VI of
the anterior cortex of adult mice and subsequently examined the
fates of dividing cells within cortex, using markers for DNA
replication (marker: 5-bromodeoxyuridine; BrdU) and progressive
neuronal differentiation. Newly produced BrdU-marker-positive
cells expressed various chemical markers of mature neurons in
regions of cortex undergoing targeted neuronal death, and these
new nerve cells survived for at least 28 weeks. The authors
report that backward labeling from thalamus to cortex (retrograde
labeling) demonstrated that the new neurons can form long-
distance cortico-thalamic connections.
     3) The authors suggest their results indicate that neuronal
replacement therapies for neurodegenerative disease and central
nervous system injury may be possible through manipulation of
endogenous neural precursors in situ, so that transplantation of
exogenous cells would not be required.
-----------
S.S. Magavi et al: Induction of neurogenesis in the neocortex of
adult mice.
(Nature 22 Jun 00 405:951)
QY: Jeffrey D. Mackis [macklis@hub.tch.harvard.edu]
-----------
Text Notes:
... ... *hippocampus: The hippocampus (plural: hippocampi) is a
region of the cerebral cortex in the medial part of the temporal
lobe. In humans, among other functions, the hippocampus is
apparently involved in short-term memory, and analysis of the
neurological correlates of learning behavior in animals indicates
that the hippocampus is also involved in memory in other species.
... ... *olfactory bulb: The olfactory relay station that
receives axons from the olfactory cranial nerve and transmits the
information via the olfactory tract to higher centers.
... ... *cerebral cortex: (cortex) The cerebral cortex is a thin
surface layering of nerve cells of the brain, the region only
several millimeters thick but covering all of the brain surface.
This is the part of the central nervous system most intimately
involved with the so-called "higher faculties", although the
cortex operates in concert with other parts of the brain. The
structure is primitive in lower mammals, and is found
progressively more pronounced and with greater surface area in
primates and man.
... ... *stem cells: In general, the term "stem cells"
refers to undifferentiated cells that upon differentiation can
give rise to various specialized cell lines such as blood cells,
skin cells, nerve cells, etc.
... ... *cortico-thalamic connections: Neural connections from
neurons in the cortex to neurons in the *thalamus.
... ... *thalamus: The thalamus is a deep brain structure that
consists of groups of nerve cells that project to various other
regions of the brain (thalamo-cortical pathways). In general,
these groups of nerve cells are specific relay stations for
sensory information (e.g., visual, auditory, pain, temperature,
etc.). Although active as a relay station to the cerebral cortex,
like most central nervous system relay stations, the thalamus
also receives feedback input from the cortex via cortico-thalamic
pathways.
... ... *apoptotic degeneration: In general, programmed cell
death produced by control mechanisms designed to destroy
defective cells.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 4Aug00
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
ON NEW NERVE CELLS IN THE ADULT HUMAN BRAIN
... In recent years... the idea that new nerve cells are not
produced in the adult human brain has effectively crumbled for at
least one specific and important brain locus called the
"hippocampus", which is a region of the cerebral cortex in the
*medial part of the temporal lobe. In humans, among other
functions, the hippocampus is apparently involved in short-term
memory, and analysis of the neurological correlates of learning
behavior in animals indicates that the hippocampus is also
involved in memory in other species.
... ... G. Kempermann and F.H. Gage (2 installations, DE US)
present a review of past and current research in adult
neurogenesis in humans, the authors making the following points:
     1) In 1965, Altman and Das reported neurogenesis in the
hippocampus of rats, in a subregion of the hippocampus called the
"dentate gyrus". But this data was not viewed as evidence of
significant neurogenesis in adult mammals, primarily because the
methods available then could not accurately estimate the number
of new neurons nor demonstrate definitively that the new cells
were indeed nerve cells. In addition, the concept of *stem cells
in the brain had not yet been introduced, and the belief was that
for new neurons to appear, the only source would be replication
(i.e., mitosis) of adult neurons. There was also no evidence that
neurogenesis occurred in non-human primates, and so the relevance
of the rat data for the human brain seemed remote.
     2) In the mid 1980s, Nottebohm discovered that neurogenesis
occurred in adult canaries in brain centers responsible for song
learning, and that the process accelerated during the seasons in
which the adult birds acquired their songs. Nottebohm and his co-
workers then demonstrated that neurogenesis also occurred in the
hippocampus of adult chickadees, particularly during seasons when
the birds had to keep track of dispersed food storage sites.
     3) In 1997, Gould and McEwan reported that some neurogenesis
occurs in the hippocampus of the primate-like tree shrew, and in
1998, these authors found the same phenomenon in marmoset
monkeys, which are classified as actual primates.
     4) Because of research difficulties, demonstration of
neurogenesis in the adult human brain had to await special
techniques. In 1998, Peter S. Eriksson reported the use of
bromodeoxyruridine as a marker for neurogenesis and the first
evidence for neurogenesis in the hippocampus of adult humans. The
use of this marker depended on its already established use as a
tumor marker in cancer patients. Bromodeoxyuridine is a marker
that becomes integrated only into the DNA of cells preparing to
divide, and the marker was in use with terminally ill patients
with cancer of the tongue or larynx. Eriksson obtained consent
from a number of patients to investigate their brains after
death, and when 5 patients died, all 5 brains displayed new
neurons in the dentate gyrus subregion of the hippocampus. At the
same time as this study was reported, other research groups
reported nerve cell production in the hippocampus of adult rhesus
monkeys, which are primates closer to humans than marmoset
monkeys.
     5) In their review, the authors refer to their own work,
noting that beginning in 1997, they have demonstrated that adult
mice given enriched living conditions generate substantial
increases in dentate gyrus hippocampal neurons over that found in
genetically identical control animals.
     6) The authors suggest that studies of neurogenesis in the
adult human brain, while difficult, may lead to better treatments
for a variety of neurological diseases. The authors conclude:
"The expected benefits of unlocking the brain's regenerative
potential justify all the effort that will be required."
-----------
G. Kempermann and F.H. Gage: New nerve cells in the adult brain.
(Scientific American May 1999)
QY: Gerd Kempermann, University of Regensburg, DE.
-----------
Text Notes: 
... ... *medial part of the temporal lobe: The temporal lobes are
roughly the lower sides of the brain, above the ears and behind
the temporal bones of the skull, but when the human brain is
viewed from the side, as it usually is in common gross
depictions, the large and functionally important ventral and
infolded parts of the temporal lobes are not visible. In general,
the larger anatomical regions of the human brain are best
visualized as highly corrugated lobular structures extensively
folded and densely packed to fit inside the volume-limiting
protective skull. Isolated verbal descriptions of the
architecture are of limited use: anatomical graphics are the best
sources for visualization of gross brain structures.
... ... *stem cells: See main report
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 18Jun99
For more information: http://scienceweek.com/swfr.htm

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

3. BIOCHEMISTRY:
AN RNA ENZYME (RIBOZYME) WITH TWO POSSIBLE FOLDS AND TWO ACTIONS
     For most of the 20th century it was firmly believed that
only proteins can act as reaction catalysts (enzymes) in
biological systems, but then in 1981 Sidney Altman, and in 1982
Thomas Cech, discovered two different RNA enzymes (ribozymes),
which are not proteins. Altman and Cech shared the Nobel Prize
for Chemistry in 1989 for their discoveries.
     Ribozymes (not to be confused with riboSOMES) are catalytic
RNA molecules that can promote specific biochemical reactions
without the need for ancillary proteins. The RNA-catalyzed
reactions can either be intramolecular (autocatalytic), e.g.,
self-splicing or self-cleaving, or intermolecular, using other
RNA molecules as substrates and involving multiple turnovers of
the ribozyme. This last case is an example of a true enzymatic
reaction, since the catalyst (the ribozyme) is recovered
unchanged after each reaction and can thus catalyze many
reactions.
... ... E.A. Schultes and D.P. Bartel (Massachusetts Institute of
Technology, US) now report a single RNA nucleotide sequence that
can assume either one of two ribozyme folds and catalyze two
respective reactions (a ligation reaction and a cleavage
reaction). The authors make the following points:
     1) The authors report the two ribozyme folds share no
apparent evolutionary history and are completely different, with
no base pairs (and probably no hydrogen bonds) in common. Minor
variants of this sequence are highly active for one or the other
reaction, and can be accessed from prototype ribozymes through a
series of neutral mutations. The implication, the authors
suggest, is that in the course of evolution, new RNA folds could
arise from preexisting folds without the need to carry inactive
intermediate sequences. The authors suggest this raises the
possibility that biological RNAs having no structural or
functional similarity might share a common ancestry, and that,
furthermore, functional and structural evolutionary divergence
might in some cases precede rather than follow gene duplication.
     2) The authors point out that their findings concerning
ribozymes raises the question of whether similar possibilities
exist in proteins. Some peptide segments can assume very
different folds within larger proteins or ribonucleoprotein
contexts. The authors point out, however, that no protein
sequence is known to autonomously assume two different enzymatic
folds and catalyze two respective reactions, and that it is
questionable whether such a protein sequence could be found. "The
chemical diversity of the 20 amino acid subunits may restrict the
conformational options of protein sequences. The 20 amino acids
have characteristic propensities to form *alpha-helical or beta-
sheet secondary structure. They also differ in water solubility,
which may explain why the most dramatic protein conformational
changes... result in insoluble aggregates. In contrast, the roles
of the 4 RNA nucleotides in forming *secondary and tertiary
structure are less specialized. Hence, the lack of chemical
diversity among the 4 RNA nucleotides, often cited as a
disadvantage for developing efficient catalysis, allows for
comprehensive conformational flexibility, leading to the
intersection of ribozyme folding [possibilities; "networks"] and
making RNA an attractive biopolymer for the birth of new
functional folds in early evolution."
-----------
E.A. Schultes and D.P. Bartel: One sequence, two ribozymes:
Implications for the emergence of new ribozyme folds.
(Science 21 Jul 00 289:448)
QY: David P. Bartel [dbartel@wi.mit.edu]
-----------
Text Notes:
... ... *alpha-helical or beta-sheet secondary structure: In
general, protein chains in biological systems fold into either
alpha-helices or beta-sheet structures. The alpha-helix is a
configuration of a peptide chain in which successive turns of the
helix are held together by hydrogen bonds between the amide
(peptide) links, the carbonyl group of any given residue being
hydrogen-bonded to the imino group of the 3rd residue behind it
in the chain. The alpha-helix was first described by Pauling and
Corey in 1951, and it has been found in proteins involved in a
wide variety of functions. In general, the beta-sheet is a
protein structure in which the polypeptide is extended and
stabilized by hydrogen bonding between NH and CO groups of
different polypeptide chains or of separate regions of the same
chain.
... ... *secondary and tertiary structure: 1) The term "primary"
structure refers to the linear structure of the polypeptide as
determined solely by the number, sequence, and type of amino acid
residues. 2) The "secondary structure" of a protein is determined
by interactions between the sequential units, particularly
hydrogen bonding between particular amino acids and nonpolar
interactions between hydrophobic regions, the interactions
producing, in general, three local or global secondary structure
variants: alpha-helix, beta-sheet, and tight-turn. The term
"tight-turn" (beta-bend; beta-turn) refers to a bending of a
short stretch of polypeptide chain that allows the main direction
of the chain to change. The turn consists of 4 amino acid
residues in which the CO group of residue n is hydrogen-bonded to
the NH group of residue (n + 3). 3) The "tertiary structure" of a
polypeptide is a 3-dimensional configuration, a folding or
coiling of the molecule primarily determined by interactions of
hydrophobic regions and to a lesser extent by hydrogen bonding.
4) The "quaternary structure" of proteins is characterized
by the interaction of 2 or more individual polypeptides, often
via disulfide bonds, the result a larger functional molecule.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 4Aug00
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
EVIDENCE THAT RNA FOLDING CAUSES SECONDARY STRUCTURE CHANGES
Biological macromolecules such as proteins and nucleic acids
assume specific higher-order configurations (tertiary structures)
that are prerequisites for their function. The standard RNA
(ribonucleic acid) folding mechanism is believed to be a 2-step
process, the RNA first folding from a primary (simple linear
polymer) into a secondary structure (e.g., a helix), which then
folds into a 3-dimensional tertiary structure stabilized by
interactions between the preformed secondary structural motifs.
Divalent metal ions bound at a few specific locations appear to
be crucial for the tertiary folding. RNA secondary structures can
be deduced by various methods, but NMR spectroscopy and x-ray
diffraction are currently the major tools for high-resolution
structure determination of RNA. ... ... M. Wu and I. Tinoco, Jr.
now report a study of secondary and tertiary structure of a
domain of a *ribozyme by nuclear magnetic resonance (NMR).
Nucleotide base pairing in aqueous solution in the absence of
magnesium ions is significantly different from the RNA in a
crystal but is consistent with thermodynamic predictions. The
authors report that on addition of magnesium ions, the RNA folds
into a tertiary structure with greatly changed base pairing
consistent with the crystal structure. The authors suggest that
the common assumption that RNA folds by first forming secondary
structure and then forming tertiary interactions from the
unpaired bases is not always correct. ... ... In a short
commentary on the Wu and Tinoco paper, D. Thirumalai points out
the following: 1) The discovery of catalytic activity in RNA
(i.e., by ribozymes) has prompted serious attempts to decipher
the mechanisms of their assembly into functional *native states
starting from linear strands. 2) Implicit in all of the proposed
folding mechanisms is the assumption that there are 2 major
structural changes in RNA en route to the native state, starting
from an ensemble of unfolded molecules. It is proposed that
stable secondary structures form rapidly, perhaps on microsecond
time scales. The subsequent assembly leading to tertiary folding
takes place by bringing the secondary structural elements
together. 3) The evidence for the 2-step process (reminiscent of
framework-like models in protein folding), namely, fast secondary
structure formation followed by slower acquisition of tertiary
interactions, came from folding studies of *tRNA. Wu and Tinoco
now show that this commonly held picture of RNA assembly may not
always be correct.
-----------
M. Wu and I. Tinoco, Jr. (2 installations, US)
RNA folding causes secondary structure rearrangement.
(Proc. Natl. Acad. Sci. US 29 Sep 98 95:11555)
QY: Ignacio Tinoco, Jr. 
-----------
D. Thirumalai (University of Maryland, US)
Native secondary structure formation in RNA may be a slave to
tertiary folding.
(Proc. Natl. Acad. Sci. US 29 Sep 98 95:11506)
QY: D. Thirumalai, University of Maryland 301-405-1000
-----------
Text Notes:
... ... *ribozyme: See main report.
... ... *native states: The "native" state or configuration of a
biological macromolecule is the functional state or configuration
ordinarily assumed by the molecule in the biological system in
which the molecule occurs.
... ... *tRNA: (transfer RNA) Transfer RNA is a class of small
RNA molecules that transfer individual amino acids to the locus
producing a growing polypeptide chain during protein synthesis.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 13Nov98
For more information: http://scienceweek.com/swfr.htm

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

4. CHEMISTRY:
SYNTHETIC RECEPTORS AND ALKALI-METAL-PI BINDING IN PROTEINS
     An argument can be made that the alkali-metal cations sodium
(Na+) and potassium (K+) are the two most important ions in
biological systems. Both ions are ubiquitous in all biological
systems, and are intimately involved in membrane transport in all
biological cells. In higher organisms, gradients in these ions
play crucial roles in the dynamics of nerve and muscle action.
And during the past 30 years, it has become apparent that the
presence or absence of these ions may dramatically affect the
activity of certain enzymes.
     Until recently, the chemical mechanism by which Na+ and K+
affect the activity of enzymes was unknown. In several proteins,
binding sites for Na+ and K+ have been identified by x-ray
crystallographic analyses, and the alkali-metal binding sites in
such proteins apparently serve two purposes: a) the bound cation
may play a structural role, in which case it is not located at
the chemically active site of the enzyme, the cation or cations
merely stabilizing a particular conformation of the protein; b)
in a second group of proteins, the alkali-metal cation(s) is
located at the active site, and it is thought that in this case
these ions are present to maintain a charge balance during the
catalytic process. 
     The solid state structures of proteins that bind alkali-
metal cations indicate that alkali-metal cations are typically
bound by polar molecular *sigma-orbital donor groups such as
carbonyl, hydroxyl, carboxylate, and water, with the oxygen(s) in
these functional groups serving as the coordinating *heteroatom.
However, evidence from calculations, gas phase studies, and
small-molecule crystal structures indicates that aromatic groups,
traditionally thought to be "hydrophobic" or "nonpolar" may also
be able to bind either Na+ or K+, so that the three aromatic
amino acids phenylalanine, tyrosine, and tryptophan may possibly
serve as *pi-orbital (pi-electron) donors for alkali-metal
cations.
... ... S.L. De Wall et al (4 authors at 2 installations, US)
present a study of alkali-metal cation-pi binding in proteins,
the authors reporting the following:
     1) The authors prepared a family of synthetic receptors that
incorporate the aromatic side chains of phenylalanine, tyrosine,
and tryptophan, with these receptors constructed around a
diaza-18-crown-6 scaffold, the ensemble serving as the primary
binding site for an alkali-metal cation.
     2) The ability of the aromatic rings to coordinate a cation
was determined by crystallizing each of the receptors in the
presence of K+ and by solving the solid state structures. In all
cases, complexation of K+ by the pi system was observed. When
possible, the structures of the unbound receptors also were
determined for comparison.
     3) Further proof that the aromatic ring makes an
energetically favorable interaction with the cation was obtained
by preparing a receptor in which the aromatic ring molecule (the
arene) was perfluorinated, reversing the electrostatics but
maintaining the aromaticity. The fluorinated arene rings do not
coordinate the cation in the solid state structure of the K+
complex, confirming the predicted consequences of electrostatic
charge reversal.
     4) The authors conclude: "The evidence presented here and
the body of data that exists on alkali-metal cation-pi
interactions clearly indicate that biological systems also may
use aromatic groups to bind cations."
-----------
S.L. De Wall et al: Synthetic receptors as models for alkali-
metal cation-pi binding sites in proteins.
(Proc. Natl. Acad. Sci. US 6 Jun 00 97:6271)
QY: George W. Gokel [ggokel@molecool.wustl.edu]
-----------
Text Notes:
... ... *sigma-orbital: In general, an "orbital" is a region
around an atomic nucleus in which there is a high probability of
finding an electron, and a "molecular orbital" is such a region
dependent on the combined fields of atomic nuclei in a molecule,
with each molecular orbital considered as formed by an overlap of
atomic orbitals. In general, "orbitals" are simplifying
theoretical approximations that assume each electron has a
definite wave function independent of the other electrons in the
system. A "sigma orbital" is any orbital completely symmetrical
about an axis between two atomic nuclei.
... ... *heteroatom: In general, "heteroatoms" are any atoms
other than carbon and hydrogen in an organic compound.
... ... *pi-orbital (pi-electron): A "pi-orbital" is a molecular
orbital with regions above and below an axis between two atomic
nuclei. In the context of this report, the important aspect of
pi-orbitals is that they involve essentially delocalized
electrons in negatively-charged space distributions (orbitals)
that can interact with positively charged ions.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 4Aug00
For more information: http://scienceweek.com/swfr.htm

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

5. MATERIALS SCIENCE:
ON THE SMALLEST RANDOM LASER
     In general, a "laser" (Light Amplification by Stimulated
Emission of Radiation) is a light amplifier commonly used to
produce monochromatic phase-locked (coherent) radiation in
specific regions of the electromagnetic spectrum.
     In an ordinary laser, light is bounced back and forth
between two mirrors that form a cavity, and after several passes
through an appropriate amplifying material in the cavity, the
amplification gain can be large enough to produce laser light. In
an ordinary laser, the emitted beam is uniquely parallel because
waves that do not bounce back and forth between the mirrors
ultimately escape through the sides without amplification.
     In a so-called "random laser", the cavity is absent, but
multiple scattering of light between particles in an appropriate
disordered material keeps the light trapped long enough for the
gain in amplification to become efficient and for laser light to
emerge in random directions.
     Since their invention in 1960, lasers have found many
important applications in both the physical sciences and
biological sciences, and they continue to be a significant focus
of research in pure and applied physics.
... ... Diederik Wiersma (Istituto Nazionale per la Fisica della
Materia-Florence, IT) presents a commentary on recent research on
ultra-small random lasers, the author making the following
points:
     1) In 1967, V.S. Letokhov predicted that the combination of
multiple scattering and light amplification would lead to a form
of laser action. But it was 25 years before random laser action
was observed experimentally by C. Gouedard et al (1993). It
became clear that the multiple scattering of light that takes
place in a disordered material does not really provide a feedback
mechanism, but it makes the light remain inside the material long
enough for the amplification to become efficient. Instead of
bouncing from one mirror to another, the light waves bounce from
one particle to another thousands of times before they leave the
disordered material. Since the multiple scattering is completely
random, the term "random laser" is used. The emission
characteristics of a random laser are similar to those of an
ordinary laser: the emission spectrum can be extremely narrow and
the output can be pulsed. But unlike an ordinary laser, a random
laser will emit randomly in all directions, just like a common
light bulb.
     2) The tiny random laser (a grain 1.7 microns in diameter)
built by H. Cao et al (Phys. Rev. Lett. 84:5584 2000; Appl Phys.
Lett. 76:2997 2000) consists of disordered clusters of zinc oxide
(ZnO) nanocrystals. After excitation by an external light source,
these zinc oxide nanocrystals provide both the amplification and
the random scattering needed for random laser action. These
crystals are also easy to make and extremely cheap: one zinc
oxide cluster costs much less than 1 cent. In addition, the laser
characteristics of these crystal clusters can be easily tuned by
varying the geometry of the clusters, and each cluster will
operate at it own specific wavelength, depending on its shape and
size.
     3) The author (Wiersma) suggests that reducing the size of a
laser source to a few microns opens up many possibilities, e.g.,
the integration of a laser within tiny optical devices. There is
an increasing effort to develop materials (called "photonic
crystals") that can guide and switch light waves in a way similar
to the manner in which electronic devices control electric
currents. A random microlaser would play the crucial role of the
active element or miniature light source in such crystals.
-----------
Diederik Wiersma: The smallest random laser.
(Nature 13 Jul 00 406:132)
QY: Diederik Wiersma [wiersma@lens.unifi.it]
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 4Aug00
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
ON THE SINGLE-ATOM LASER
In general, resonance is a marked increase in the oscillation
amplitude of a system when the system is subjected to an
oscillating force whose frequency is the same or close to the
natural frequency of the system as determined by the system
parameters. The phenomenon occurs in all systems, including
optical systems. Coherent light waves are light waves of similar
phase, direction, and amplitude, and a laser (light amplification
by stimulated emission of radiation) is a device that converts
input power into a very narrow intense beam of coherent visible
or infrared light, the conversion mechanism essentially involving
excitation of atoms to a higher energy state producing resonator-
forced in-phase radiation. The power output of lasers depends on
the physical constraints, the number of excited entities
involved, the types of entities involved, etc., and the possible
power output ranges over a large spectrum. For example, the
neodymium-YAG laser (neodymium-yttrium-aluminum-garnet laser) has
a power output of the order of 1 watt and is useful for surgery;
the helium neon laser has a power output of the order 10^(-3)
watts and is used in such devices as bar-code scanners; the
microcavity semiconductor laser has a power output of the order
of 10^(-4) watts and is expected to have applications in future
optical computers now in the developmental stage; the singe-atom
laser has a power output of the order of 10^(-11) watts and is
primarily an experimental tool, but it may also find applications
in low-noise information processing and precision spectroscopy.
... ... Feld and An (2 installations, US KR) review their own
work on the single-atom laser and make the following points:
1) The light generated by the single-atom laser exhibits
properties that can be explained only by quantum mechanics, and
it can be used to test the predictions of quantum theory and to
gain new insight into the nature of laser light. 2) The basis of
the single-atom laser device used by the authors is the process
known as quantized Rabi oscillation. The physicist I.I. Rabi
(1898-1988) studied in the 1930s the periodic exchange of energy
between atoms and an electromagnetic field (e.g., radio waves),
and the process came to be called "Rabi oscillation". In free
space, an excited atom will spontaneously emit a photon in a
random direction. In a resonant cavity, the temporal
characteristics of the emission are altered, a process known as
"vacuum Rabi oscillation", and if another excited atom enters the
cavity to be affected by the emitted photon from the first atom,
the process known as "quantized Rabi oscillation" occurs, and the
second atom emits an identical photon in the same direction as
the first but at a faster rate. [Editor's note: All of these
events are occurring within the domain of quantum
electrodynamics, and brief verbal descriptions of the events
without the relevant defining equations are seriously
handicapped.] In their review, the authors outline part of their
program for future experiments, and they conclude that the
single-atom laser may assist in the future development of
semiconductor lasers by improving our understanding of
quantum-mechanical phenomena.
-----------
QY: Michael S. Feld, Mass. Inst. of Technology 617-253-1000.
(Scientific American July 1998) (Science-Week 10 Jul 98)
For more information: http://scienceweek.com/swfr.htm

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

6. EXPERIMENTAL PHYSICS:
ON EXCEEDING THE VELOCITY OF LIGHT
     The term "absolute refractive index" (refractive constant)
refers to the ratio of the speed of electromagnetic radiation in
free space to the speed of the radiation in a particular medium,
with the refractive index varying with the wavelength of the
radiation. (The term "relative refractive index" refers to ratio
of the speed of electromagnetic radiation in one medium to that
in an adjacent medium.)
     In general, the term "dispersion" refers to the
decomposition of a beam of white light into colored beams that
spread out to produce a spectrum. More specifically, dispersion
is concerned with descriptions of the variation of refractive
index with wavelength.
     Ordinary (normal) dispersion is exhibited by most
transparent substances, which show increasing refractive index
with decreasing wavelength, the variation being greater at
shorter wavelengths.
     The term "anomalous dispersion" refers to marked changes in
the curve relating refractive index to wavelength when the
wavelength is near the absorption bands of the material. On the
longer wavelength side of the absorption band, the refractive
index is high; on the shorter wavelength side of the absorption
band, the refractive index is low. Hence, the adjective
"anomalous".
     An experimental "light pulse" has a finite duration, and in
theory (the so-called "bandwidth theorem") this requires an
infinite number of waves of different frequency to be added
together. The shorter the desired pulse, the larger the bandwidth
of frequencies that must be used. Theoretically, all light pulses
are therefore formed by a packet of waves of different frequency,
each of which has a different amplitude and phase. The speed of
individual waves is called the "phase velocity", and the velocity
at which the peak of the wave packet propagates is called the
"group velocity". In a vacuum, the phase and group velocities are
identical, but in a highly absorbing or dispersive medium the
phase and group velocities are usually different. A so-called
"negative group velocity" results when the phases of the
different frequency components are shifted by the medium through
which they travel in a way such that the wave packet they form at
the exit is brought forward in time compared with the same pulse
traveling through a vacuum.
     During the past two decades, using various techniques,
researchers have demonstrated the transmission of certain light
pulses over short distances with apparent velocities greater than
the speed of light (c =~ 3 x 10^(8) meters per second) in a
vacuum, the effect known as "superluminal light propagation". The
experimental conditions are extremely specific, and the results
difficult of general interpretation. But despite ballyhoo in the
popular media concerning these experiments, the rule in physics
remains intact: no mass can travel faster than (c), and no
information or signal can be transmitted faster than (c). Any
violation of this rule would imply a violation of both Einstein's
theory of special relativity and the principle of causality --
and the rule has not yet been demonstrated to be violated
anywhere.
... ... L.J. Wang et al (3 authors at NEC Research Institute, US)
present a report of experiments on superluminal light
propagation, the authors making the following points:
     1) The authors report the use of gain-assisted linear
anomalous dispersion to demonstrate superluminal light
propagation in atomic cesium gas, with the group velocity of a
laser pulse of wavelength near the absorption line of the medium
exceeding (c) and even becoming negative, while the shape of the
pulse is preserved. The authors report they measured a group
velocity index of -310(+-5), which in practice "means that a
light pulse propagating through the atomic vapor cell appears at
the exit side so much earlier than if it had propagated the same
distance in a vacuum, that the peak of the pulse appears to leave
the cell before entering it." The authors suggest the observed
superluminal light pulse propagation is not at odds with
causality, since it is "a direct consequence of classical
interference between its different frequency components in an
anomalous dispersion region [of the curve relating refractive
index to wavelength]."
     2) In a commentary on this work in the same journal, Jon
Marangos (Imperial College London, UK) states: "Traditionally,
the signal velocity of a light pulse is defined as the speed at
which the half peak-intensity point on the rising edge of the
waveform travels; in [the Wang et al] experiment, this is clearly
superluminal. In contrast, some researchers argue that the true
speed at which information is carried by a light pulse is not the
group velocity of a smooth pulse, but rather the speed at which a
sudden step-like feature in the waveform travels, which so far
has not been shown to exceed (c)."
-----------
L.J. Wang et al: Gain-assisted superluminal light propagation.
(Nature 20 Jul 00 406:277)
QY: L.J. Wang [Lwan@research.nj.nec.com]
-----------
Jon Marangos: Faster than a speeding photon.
(Nature 20 Jul 00 406:243)
QY: Jon Marangos [j.marangos@ic.ac.uk]
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 4Aug00
For more information: http://scienceweek.com/swfr.htm

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

7. FOCUS REPORT: ON THE OLDEST LIFE ON EARTH
"Reconstructing conditions on the early Earth is difficult and
challenging. Rocks older than 3.5 billion years are very rare on
Earth. There may have been only tiny patches of continental crust
on the early Earth; over 90 percent of the crust would have been
oceanic rock that has long been destroyed. The oldest minerals on
Earth are zircon crystals over 4 billion years old, but they have
been eroded out of their original rocks and deposited as
fragments in younger rocks. The oldest known rocks are in the
Isua area of West Greenland, and have been dated by several
methods at about 3850 million years ago. The rocks include
sedimentary formations. Although they have been repeatedly
folded, faulted, and reheated, the Isua sediments can still tell
us something about conditions on the early Earth when they were
formed. They were laid down in shallow, nearshore water, and they
include beach-rounded pebbles and weathering products from
volcanic lava. Temperatures at the time may have been warm, but
they were not extraordinary. The shoreline was probably volcanic
and tropical. The Isua rocks contain quite a lot of carbon in the
form of mineral graphite. When CO(sub2) is taken up by
[biological] cells, used in photosynthesis, and incorporated in a
cell, the light isotope carbon-12 is slightly enriched over the
heavier isotope carbon-13, enough to convince many geochemists
that it once went through photosynthesis inside a cell. Thus
there is indirect evidence that there may have been life on Earth
at or before 3850 million years ago. There is clearer isotopic
evidence for biological carbon (life) at 3.7 billion years ago.
The first fossils came from later rocks."
-----------
Richard Cowen: _History of Life_
(Blackwell Science Inc., London 2000, p.27)

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

8. FROM THE SW ARCHIVE:
ON THE PHYSICIST MARIA GOEPPERT-MAYER
In general, the isotope effect refers to differences in
reactivity of a compound when in the compound one isotope of an
element is substituted for another isotope of the element. The
carbon-hydrogen bond energy, for example, is less than that of
the carbon-deuterium bond energy, so reactions involving the
breaking of these bonds will differ in various parameters. The
effect, apparently involving differences in vibrational energies
of the isotopes, differences that in turn are mostly dependent on
differences in isotope masses, was first described in a quantum
mechanical formulation in a classic paper by Jacob Bigeleisen and
Maria Goeppert-Mayer in 1947. Maria Goeppert-Mayer (1906-1972) is
one of the more interesting personages of 20th century science.
She received her PhD in physics at the University of Gottingen in
1930, emigrated to the US in 1933, married the chemist Joseph
Mayer, as a woman was consistently refused employment by American
universities except at levels of that of a teaching assistant,
and she more or less worked independently until the 1940s. But
her brilliance was eventually recognized, she was part of the
Columbia University Manhattan Project (working with Bigeleisen),
she later assisted Enrico Fermi, and she eventually won a Nobel
Prize in Physics in 1963 for her shell model of the atomic
nucleus, which supposedly she devised in 10 minutes while sitting
in Fermi's office at the University of Chicago. She is one more
example of a brilliant woman denied a solid career in science for
reasons that seem absurd. She was finally appointed Professor of
Physics at the University of California San Diego in 1960. In
chemistry, the applications of the isotope effect have been
profound, and all chemists are aware of her classic paper with
Bigeleisen, who after 1947 continued work in the field,
particularly on kinetic isotope effects. To celebrate the 50th
anniversary of the influential paper by Bigeleisen and
Goeppert-Mayer, the Journal of Chemical Physics, in which the
paper first appeared in 1947 (15:261), has authorized a
reprinting of the original to be distributed to participants at
the forthcoming Gordon Research Conference on Isotopes in
Biological and Chemical Sciences. Bigeleisen has stated the
original isotope effect formulation was in fact due to a flash of
insight by Goeppert-Mayer, and an argument can be made that
Goeppert-Mayer deserved a Nobel Prize in chemistry as well as one
in physics.
(Chem. & Eng. News 22 Dec 97) (Science-Week 2 Jan 98)

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
 
NOTICES  
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-= 

CHANGE OF EMAIL ADDRESS:
If at any time you need to change the Email address at which you
receive SW, please send the information to:
request@scienceweek.com

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

SCIENCE-WEEK SUBSCRIPTIONS:
Subscriptions to ScienceWeek cost as little as US$15 a year.
Complete subscription information is available at:
http://scienceweek.com/subinfo.htm

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

The first issue of SCIENCE-WEEK appeared May 1, 1997, and it has
been published regularly each week since that date. SW is
designed to cross existing conceptual and linguistic barriers
between the scientific disciplines. In general, the biology is
written for physicists and chemists, and the physics and
chemistry are written for biologists, with an attempt to retain
some exactitude in the particular science involved in the news.
These are the aims. Undoubtedly, we are not always successful,
and for that we apologize. In any case, what we hope is that our
readers are reading out of their fields more than in their
fields, since that is the essence of this publication.

We welcome comments, suggestions, and criticisms from our
subscribers. Public letters relevant to any report are also
welcome. Editorial contact: [editors@scienceweek.com].

Editor/Publisher: Dan Agin
Managing Editor: Claire Haller
Associate Editor: Joan Oliner

Copyright (c) 1997-2000 SCIENCE-WEEK/Spectrum Press Inc.
All Rights Reserved

---------------------------------------------
This publication is protected by U.S. and International Copyright
Laws, and no display, transmission, or duplication in any medium,
including BBS, Internet Email, website duplication, fax, or print
is permitted without the explicit consent of the holder of the
copyright. SCIENCE-WEEK is published by Spectrum Press Inc.,
3023 N. Clark Street #109, Chicago, 60657-5205 IL, USA.
---------------------------------------------
-----end file