|
ScienceWeek
SCIENCE-WEEK - March 22, 2002 - Vol. 6 Number 12
An Email Research Digest Published Weekly Since 1997
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-
--------------------------------------------------
The chemists are a strange class of mortals who seek
their pleasures among soot and flame, poisons and
poverty... yet among all these evils I seem to live
so sweetly... may I die if I would change places
with the Persian King.
-- John Joachim Becher, alchemist, ca. 1650
--------------------------------------------------
=-=-=-=-=-=-=-=-=
Section 1
=-=-=-=-=-=-=-=-=
Contents of this Issue (Full reports in Section 2):
[(*) = includes background reports]
Basic Sciences
--------------
1. Discovery of Remarkable Memory in Sheep
2. On Dielectric Relaxation in Enzymes
3. Genome Sequence of the Causative Agent of Plague (*)
4. Mitochondrial DNA and Disease (*)
5. On Eukaryotic DNA Replication
6. The Elusive Neanderthals
7. On the Persistent Radical Effect in Chemical Systems
8. On the Engineering of Supramolecular Crystals (*)
9. Charge Transfer and the Isomer Effect
10. Biophysics: Oscillating Proteins and Bacterial Cell Division
11. Physical Chemistry: The Glass Transition of Water
12. Vibrational Control in Chemical Reactions
Praxis
------
13. Use of Bacteria in Therapy Against Tumors
14. Genetic Diversity and Disease
15. Effects of Maternal Cigarette Smoking (*)
16. Health Care and Rural America
17. Diabetes and Microvascular Pathology
18. Prevalence of Celiac Sprue
19. Global Warming, Sea-Level Rise, and Loss of Coastal Wetlands
20. On Energy Sources
21. On Enzymatic Polymerization
22. Semiconductor Lasers and Delayed Optical Feedback
23. On Charge Transport in DNA
24. On Mixing in Microchannels
Miscellany
----------
25. In Focus: On James Clerk Maxwell (1831-1879)
26. From the SW Archive: Cell Biology: On Prokaryotes
=-=-=-=-=-=-=-=-=
Section 2
=-=-=-=-=-=-=-=-=
1. DISCOVERY OF REMARKABLE MEMORY IN SHEEP
K.M. Kendrick et al (Babraham Institute, UK) discuss memory in
sheep, the authors making the following points:
1) The human brain has evolved specialized neural mechanisms
for visual recognition of faces, which afford us a remarkable
ability to discriminate between, remember, and think about many
hundreds of different individuals. Sheep also recognize and are
attracted to individual sheep and humans by their faces, as they
possess similar specialized neural systems in the temporal and
frontal lobes for assisting in this important social task,
including a greater involvement of the right brain hemisphere.
2) The authors report a demonstration that individual sheep
can remember 50 other different sheep faces for over 2 years, and
that the specialized neural circuits involved maintain selective
encoding of individual sheep and human faces even after long
periods of separation.
3) The authors report they trained 20 sheep (Ovis aries) to
discriminate in a choice maze between pictures showing frontal
views of 25 pairs of sheep faces by associating one member of
each face pair with a food reward. Animals required 30 or more
trials to reach a learning criterion of over 80 percent correct
choice, and were given a further 400 to 500 trials over a period
of 4 to 6 weeks. These latter trials confirmed that these sheep
could also discriminate between profile views of the same
individuals without having to relearn the task. The authors then
tested the sheep for retention of discrimination performance
after delays of up to 800 days. Sheep could still discriminate
accurately between the 25 face pairs at all retention time
points. Only after 601 to 800 days was retesting performance
significantly poorer than final original levels.
-----------
Nature 2001 414:165
-----------
ScienceWeek 22 Mar 2002 www.scienceweek.com
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
2. ON DIELECTRIC RELAXATION IN ENZYMES
G. Archontis and T. Simonson (University of Cyprus, CY) discuss
dielectric relaxation in enzymes, the authors making the
following points:
1) Many chemical events in proteins involve charge
separation or charge transfer: enzymatic reactions,
photoexcitation of bound chromophores, electron transfer, proton
binding and release, and binding of metal ions and other charged
ligands. In response to such an event, the protein and solvent
relax, or reorganize, both through electronic polarizability and
through the motions of charged and polar groups of atoms. This
relaxation is a key component of protein energetics. A striking
example is provided by electron transfer in cytochrome c between
ruthenated histidines, introduced artificially at the protein
surface, and the central heme group. The corresponding
reorganization energy is approximately 1 eV, which is comparable
to the redox potential difference spanned by the entire
respiratory chain in cells.
2) In general, an important feature of enzyme reactions is
the limitation of undesired dielectric relaxation, especially for
proton- and electron-transfer steps. Indeed, the low
polarizability of the protein interior compared to solvent helps
to reduce activation barriers and increase catalytic rates, and
is one of the most fundamental physical properties of proteins.
3) Computer simulations have demonstrated that dielectric
relaxation in proteins is very complex, involving both protein
and solvent degrees of freedom and including both fast local and
slow collective motions. Several experimental studies have
involved spectroscopic probes whose optical absorption and
emission are sensitive to the dielectric properties of the
environment, but the experimental interpretation is rarely
straightforward, since it is extremely difficult to separate the
solvent and protein response without resorting to simulations.
-----------
J. Am. Chem. Soc. 2001 123:11047
-----------
ScienceWeek 22 Mar 2002 www.scienceweek.com
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
3. GENOME SEQUENCE OF THE CAUSATIVE AGENT OF PLAGUE
J. Parkhill et al (Wellcome Trust Genome Center, UK) discuss the
genome sequence of the plague pathogen, the authors making the
following points:
1) The Gram-negative bacterium Yersinia pestis is the
causative agent of the systemic invasive infectious disease
classically referred to as "plague", and this pathogen has been
responsible for 3 human pandemics: the Justinian plague (6th to
8th centuries), the Black Death (14th to 19th centuries), and
modern plague (19th century to the present day).
2) The recent identification of Y. pestis strains resistant
to multiple drugs and the potential use of Y. pestis as an agent
of biological warfare signify that plague still poses a threat to
human health.
3) The authors report the complete genome sequence of Y.
pestis strain CO92, consisting of a 4.65-megabase chromosome and
3 plasmids of 96.2 kilobases, 70.3 kilobases, and 9.6 kilobases.
The authors report the genome is unusually rich in insertion
sequences and displays anomalies in guanine-cytosine base
composition bias, indicating frequent genomic recombination. Many
genes of the genome seem to have been acquired from other
bacteria and viruses (including adhesins, secretion systems, and
insecticidal toxins). The genome contains approximately 150
pseudogenes, many of which are remnants of a redundant
enteropathogenic lifestyle. The authors suggest that the evidence
of ongoing genome fluidity, expansion, and decay, suggests Y.
pestis is a pathogen that has undergone large-scale genetic flux,
and that the genome of this pathogen provides a unique insight
into the ways in which new and highly virulent pathogens evolve.
-----------
Nature 2001 413:523
----------
Related Background:
MEDICAL BIOLOGY: PLAGUE AS A BIOLOGICAL WEAPON
Plague, also called bubonic plague or "Black Death", is a disease
with a notorious history. It is caused by the rod-shaped
bacterium (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.
... ... T.V. Inglesby et al (19 authors at 10 installations, US)
present a review of medical and public health considerations of
plague as a biological weapon, the authors making the following
points:
1) In 541 AD, the first recorded plague pandemic began in
Egypt and spread across Europe with consequent population losses
of 50 to 60 percent in North Africa, Europe, and central and
southern Asia. The second plague pandemic, also known as the
"Black Death" or "Great Pestilence", began in 1346 and eventually
killed 20 to 30 million people in Europe, approximately one-third
of the European population of that time. Plague spread slowly and
inexorably from village to village by infected rats and humans or
more quickly from country to country by ships. This second
pandemic lasted more than 130 years and had major political,
cultural, and religious ramifications. The third pandemic began
in China in 1855, spread to all inhabited continents, and
ultimately killed more than 12 million people in India and China
alone. Small outbreaks of plague continue to occur throughout the
world.
2) Advances in living conditions, public health, and
antibiotic therapy have made future pandemics of plague
improbable, but plague outbreaks following use of a biological
weapon are a plausible threat. In World War II, a secret branch
of the Japanese army ("Unit 731") is reported to have dropped
plague-infected fleas over populated areas of China, thereby
causing outbreaks of plague. In subsequent years, the biological
weapons programs of the US and the Soviet Union developed
techniques to aerosolize plague directly, eliminating dependence
on the unpredictable flea vector. In 1970, the World Health
Organization (WHO) reported that, in a worst-case scenario, if 50
kilograms of the plague pathogen Y. pestis were released as an
aerosol over a city of 5 million people, pneumonic plague could
occur in as many as 150,000 persons, 36,000 of whom would be
expected to die. The plague bacilli would remain viable as an
aerosol for 1 hour for a distance of up to 10 kilometers.
Significant numbers of inhabitants might attempt to flee, further
spreading the disease.
3) Although US scientists did not succeed in making
quantities of plague organisms sufficient for use as an effective
weapon by the time the US offensive program was terminated in
1970, Soviet scientists were able to manufacture large quantities
of the agent suitable for placing into weapons. More than 10
institutes and thousands of scientists were reported to have
worked with plague in the former Soviet Union.
4) There is little published information indicating actions
of autonomous groups or individuals seeking to develop plague as
a weapon. However, in 1995 in Ohio (US), a microbiologist with
suspect motives was arrested after fraudulently acquiring Y.
pestis by mail. New US antiterrorism legislation was introduced
in reaction to this incident.
5) The authors conclude: "An aerosolized plague weapon could
cause fever, cough, chest pain, and *hemoptysis with signs
consistent with severe pneumonia 1 to 6 days after exposure.
Rapid evolution of disease would occur in 2 to 4 days after
symptom onset and would lead to septic shock with high mortality
without early treatment."
-----------
J. Amer. Med. Assoc. 2000 283:2281
-----------
Notes:
... ... *hemoptysis: (bronchostaxis) Spitting of blood derived
from the lungs or bronchial tubes as a result of pulmonary or
bronchial hemorrhage.
-----------
ScienceWeek 22 Mar 2002 www.scienceweek.com
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
4. ON MITOCHONDRIAL DNA AND DISEASE
R.E. Broughton et al (University of Oklahoma, US) discuss
mitochondrial DNA, the authors making the following points:
1) Mitochondria provide the primary source of cellular ATP
in eukaryotes via the process of oxidative phosphorylation. In
animals, extranuclear mitochondrial genomes are typically
circular, and with few exceptions code for 13 subunits of the
oxidative phosphorylation machinery as well as for genes for 2
ribosomal RNA subunits and 22 transfer RNAs.
2) Mutations in mitochondrial DNA have a number of known
deleterious effects. At least 50 base substitutions and hundreds
of insertion/deletion mutations have been identified in human
mitochondrial DNA, with effects ranging from degenerative
diseases to aging to cancer. In addition to their role as the
powerhouse of the cell, mitochondria are also involved in
regulating programmed cell death (apoptosis), and mutagenic
reactive oxygen species are generated in the process of energy
production. Pathologies can result directly from the loss of ATP
production in affected tissues, the buildup of oxygen radicals
due to downstream blockage of the oxidative phosphorylation
pathway, or unregulated apoptosis.
3) Hundreds of mitochondria and thousands of mitochondrial
DNAs are inherited maternally through the cytoplasm of the
oocyte. If a zygote receives more than one form of mitochondrial
DNA (heteroplasmy), different forms can be randomly distributed
to daughter cells during cell division, and over many cell
generations these different forms can drift to high or low
frequency in various cell lineages. Thus, if one of the mutant
forms is deleterious, disease may affect lineages where it
reaches sufficiently high frequency.
-----------
Genome Research 2001 11:1958
----------
Related Background:
MEDICAL BIOLOGY: MITOCHONDRIA IN HUMAN DISEASE
Mitochondria are double-membrane enclosed organelles of
cells that are involved with several important biochemical
pathways, including *electron transport and *oxidative
metabolism. Various types of eukaryotic cells (i.e., cells
containing membrane-bound organelles) may contain from a few to
several thousand mitochondria in each cell type. The mitochondria
are relatively large cylindrical structures up to 10 microns long
and up to 2 microns in diameter, and they are believed to have
originated as organisms that became *symbiotic with eukaryotic
cells.
In general, the term "apoptosis" refers to programmed cell
death, whether as a part of normal tissue differentiation and
development, or as a program activated in a defective cell. In
the molecular biology of cancer, apoptosis is the name given to
the programmed cell death provoked by certain proteins expressed
by *tumor suppressor genes. Thus, malignant cells are defective
cells with a deactivated apoptosis program, and this allows
malignant cells to survive and replicate. In most tissues within
the body, a delicate balance is maintained between cell
proliferation and cell death. Aging or damaged cells are replaced
with new cells, ensuring that tissues are maintained in prime
condition. If this balance is disturbed in either direction, the
consequences can be severe. Tissue degeneration will occur if
cell death predominates over cell proliferation, and when cell
proliferation outstrips cell death, the result is the development
of tumors.
In recent years, it has been discovered that mitochondria
play a central role in the apoptosis process, this in addition to
their well-established role of providing *adenosine triphosphate
(ATP) to drive the energy-requiring processes within the cell.
... ... Anne Murphy (MitoKor, US) reviews recent research on the
role of mitochondria in human disease, the author making the
following points:
1) Mitochondrial dysfunction is an apparent underlying
contributor to many diseases. It has long been known that the
lack of mitochondrial ATP production can lead to necrotic death
in many pathologies, including *ischemia/reperfusion injury and
*toxin exposure. More recently, it has become apparent that
apoptosis can be induced by a wide variety of events, many of
which involve the release of "apoptogens" (e.g., *cytochrome c
and *caspases) from mitochondria. Often these stimuli initiate a
caspase-dependent cascade of *proteolysis from which cells
generally do not recover.
2) Forms of apoptosis exist that may not be dependent on
mitochondrial apoptogen release. These forms of apoptosis appear
to involve responses to certain *inflammatory mediators that bind
specific death receptors. The extent to which mitochondria play a
role in these varieties of cell death may be dependent upon cell
type and the level of expression of specific caspases.
3) There are numerous diseases with components of apoptosis,
but notable among these are certain neurodegenerative diseases,
ischemic/reperfusion injury, autoimmune disorders and
inflammatory diseases (including arthritis), and viral infection
(including human immunodeficiency virus [HIV])). Also, the
development of certain cancers is apparently associated with the
loss of appropriate levels of apoptosis. Furthermore, in cancer,
resistance of malignant cells to chemotherapeutic agents is
associated with the expression of proteins, localized to
mitochondria, that inhibit apoptosis.
4) Clinical studies have implicated mitochondrial
dysfunction in certain chronic diseases, including *Alzheimer's,
*Huntington's, and *Parkinson's diseases. There is evidence of
metabolic abnormalities in the rates of *glucose utilization and
*lactate production in the affected brain regions of patients
with these diseases. There is also evidence of a decrease in the
maximal activity of *electron-transport-chain complexes in the
brains or peripheral tissues of patients with these diseases. The
question is whether these defects are sufficient to compromise
normal neuronal function, and whether they are the cause or the
result of the respective disease.
-----------
The Biochemist April 2000
-----------
Notes:
... ... *electron transport: This refers to a sequence of steps
in the final stage of the aerobic respiration biochemical pathway
in which high energy electrons are effectively passed through a
series of membrane-bound carrier molecules to support a proton
gradient involved in energy storage. The term "transport" here
refers essentially to a chemical flow diagram and not necessarily
to an actual spatial translocation of electrons.
... ... *oxidative metabolism: In general, a set of biochemical
pathways dependent on the utilization of supplied oxygen.
... ... *symbiotic: In biology, "symbiosis" is an intimate and
protracted association of individuals of different species.
... ... *tumor suppressor genes: In general, cancer genes have
been divided into 2 classes, proto-oncogenes and tumor suppressor
genes. Proto-oncogenes are genes that sustain activating changes
in human cancer. These changes may take the form of point
mutations or gene rearrangements that lead to increased or
uncontrolled activity of the encoded protein, or they make take
the form of gene amplification, which results in increased levels
of protein expression. In contrast, tumor suppressor genes are
characterized by inactivating changes in human cancer, typically
point mutations that result in truncation or functional
inactivation of the encoded protein, or gross deletions of
chromosomal fragments carrying these genes.
... ... *adenosine triphosphate (ATP): ATP is the most important
chemical energy source in all living cells, intimately involved
in various cell functions and cell metabolism, and an entity in
numerous cyclic chemical pathways involved in the synthesis of
various cell components.
... ... *ischemia/reperfusion injury: In general, "ischemia" is a
sudden loss of blood supply to a tissue caused by blockage of a
blood vessel. The term "ischemia/reperfusion injury" refers to
the damage that can occur to a tissue when it is reperfused after
a prolonged period of ischemia. The phenomenon is of considerable
clinical importance, especially in connection with heart attacks
and strokes.
... ... *toxin: In general, any noxious or poisonous substance,
especially substances produced by living systems.
... ... *cytochrome c: The cytochromes, categorized as
hemoproteins with differing porphyrin groups, are widely
distributed respiratory (oxygen-utilizing) catalysts involved in
the electron transport chain of living cells. They do not combine
with substrates, but alternate between Fe(2+) and Fe(3+) states.
There are various cytochromes, with cytochrome c present in the
greatest amounts, and most importantly in the mitochondria of
eukaryotic cells.
... ... *caspases: Proteases are a class of enzymes that
hydrolyze proteins, splitting them into various groups of
subunits, with the sites of hydrolysis dependent on the
particular enzyme and the protein substrate, and a caspase is a
type of protease implicated in apoptosis.
... ... *proteolysis: In general, hydrolysis (breakdown) of
proteins.
... ... *inflammatory mediators: In general, an "inflammatory
change" is a response of tissues to irritation or injury. The
response involves a dynamic complex of cellular and chemical
reactions that occur in the affected blood vessels and adjacent
tissues.
... ... *Alzheimer's, *Huntington's, and *Parkinson's diseases:
All three of these neurodegenerative diseases involve
considerable loss of nerve cells in certain areas of the brain.
... ... *glucose utilization: In biological systems, glycolysis
(also known as Embden-Meyerhof pathway), involving the breakdown
of glucose, is one of the main energy producing pathways in the
cell.
... ... *lactate production: Lactate is a salt or ester of lactic
acid, and lactic acid is a common end product of glycolysis in
biological systems.
... ... *electron-transport-chain complexes: The term "electron-
transport chain" (respiratory chain) refers to the sequence of
reactions involving enzymes and other proteins within the
mitochondrion by which substrates are oxidized.
-----------
Related Background:
MOLECULAR BIOLOGY: APOPTOSIS, MITOCHONDRIA, AND CASPASES
Apoptosis (programmed cell death) is a rapid and specific process
involving the production of a number of enzymes in the cell
programmed to be destroyed. This programmed destruction is not
always harmful, or always the result of cellular damage of one
sort or another. In humans, for example, the lack of webbing
between fingers and toes is a result of apoptosis of cells of
webbing tissue occurring during embryological development, the
apoptosis in this case being a normal part of the larger
embryological program. In the mature organism, apoptosis is the
usual method of removing damaged cells after these cells are
recognized to be damaged by one mechanism or another. It is known
that normal cells carry an apoptosis receptor on their surfaces,
called CD95, and that when this surface receptor is cross-linked
by its specific ligand, this triggers the sequence of events
known as apoptosis. In the apoptosis sequence, certain
*proteolytic enzymes inside the cell are activated, and in
addition a variety of lipids that cause cell dysfunction are
synthesized.
... ... D.R. Green and J.C. Reed review the involvement of
*mitochondria with apoptosis in *metazoan cells, and the authors
make the following points: 1) The current consensus among
biologists is that approximately 2 billion years ago the cells
destined to become the ancestors of all *eukaryotes entered into
a partnership with an ancestor of today's *purple bacteria, an
ancestor that subsequently became the mitochondria of today. 2)
It has been hypothesized by several investigators that the
*endosymbiotic origins of mitochondria and the evolution of
aerobic metabolism in eukaryotes formed the basis for the
evolution of active cell death, which in metazoans is manifested
predominantly as apoptosis. Central roles for mitochondria as the
orchestrators of apoptosis have been firmly established in many
systems. 3) In recent years it has become apparent that the
effectors of apoptosis are a family of intracellular proteases
known as caspases, although inhibiting these enzymes does not
always prevent apoptosis. 4) At least 3 general mechanisms have
been proposed for the involvement of mitochondria in the control
of cell life and death: a) disruption of *electron transport,
*oxidative phosphorylation, and adenosine triphosphate (ATP)
production; b) release of proteins that trigger activation of the
caspases family of proteases; c) alteration of cellular *redox
potentials. 5) In many apoptosis scenarios, the mitochondrial
inner electrical transmembrane potential collapses, indicating
the opening of large conductance channels through the inner
membrane. In contrast, certain stimuli can induce rupture of the
outer membrane of mitochondria and release of caspase-activation
proteins. The authors conclude: "Perhaps a few hundred million
years ago, either convergent or divergent evolutionary processes
allowed the ... fundamental framework for bacterial warfare to be
incorporated into the cell death mechanisms used by animal cells,
thereby establishing mitochondria as important participants not
only in animal cell life but also in active cell death."
... ... In a companion and contiguous review of caspases and
apoptosis, N.A. Thornberry and Y. Lazebnik point out the
following: 1) Proteolysis is irreversible, which implies that
regulation of proteases is limited to control of their activity
and availability of substrate -- the only known way of
"correcting" a cleaved protein is to make it afresh. 2) Most
proteases are synthesized as precursors that have little if any
catalytic activity. The precursor is usually converted to the
active enzyme by proteolytic processing mediated either by
another protease or by autocatalysis. Thus large amounts of
precursor can be accumulated in advance and activated on demand.
3) Proteases can regulate their own activation, resulting in an
exponential rate of activation. 4) Where there are proteases
there are inhibitors, and these inhibitors regulate the
concentration of active protease in the cell. 5) Proteolytic
reactions can be specific, determined by a combination of
primary, secondary, or tertiary structures of protein substrates.
Proteolysis that governs critical biological processes such as
the cell cycle or cell death is highly specific and involves a
restricted set of substrates. 6) The various caspases share
similarities in amino acid sequence, structure, and substrate
specificity. 7) Caspases are among the most specific of proteases
with an unusual and absolute requirement for cleavage after
aspartic acid and recognition of at least 4 amino acids terminal
to the cleavage site. 8) The strict specificity of caspases is
consistent with the observation that apoptosis is not accompanied
by indiscriminate protein digestion, but rather a select set of
proteins is cleaved in a coordinated manner, usually at a single
site, resulting in a loss or change in function. 9) Apoptotic
events include DNA fragmentation, *chromatin condensation,
*membrane blebbing, cell shrinkage, and disassembly into
membrane-enclosed vesicles (apoptotic bodies). In vivo, this
process culminates with the engulfment of apoptotic bodies by
other cells, preventing complications that would result from a
release of intracellular contents. In apoptosis, these changes
occur in a predictable reproducible sequence and can be completed
with 30 to 60 minutes. The authors conclude: "Substantial
progress has been made in understanding the structural and
catalytic properties of active caspases and their contribution to
apoptosis. The goal for future research is to understand the
regulation of these enzymes. This should facilitate efforts to
rationally manipulate the apoptotic machinery for therapeutic
gain."
-----------
Science 1998 281:1309,1312
-----------
Notes:
... ... *proteolytic enzymes: These enzymes, also called
"proteases", split proteins and thereby degrade them. The enzymes
catalyze the hydrolysis of peptide bonds, fragmenting proteins
into polypeptide chains, and fragmenting polypeptide chains into
constituent amino acids. Sometimes proteolytic enzymes and
proteases are distinguished, with the term "proteases" reserved
for proteolytic enzymes with high specificity for peptide bonds
between particular amino acids.
... ... *mitochondria: See main report.
... ... *metazoan cells: Metazoans are multicellular animals.
... ... *eukaryotes: Cells (and organisms consisting of such
cells) that contain intracellular membrane-bound compartments
such as a nucleus (membrane-bound "organelles").
... ... *purple bacteria: Specifically, any of the various
photosynthetic bacteria that contain bacteriochlorophyll, and are
thus distinguished by purplish or reddish-brown pigments. But the
term "purple bacteria" is sometimes used as a synonym for the
phylum Proteobacteria, a general category comprising a large
number of diverse forms.
... ... *endosymbiotic: Endosymbiosis is an arrangement in which
one organism lives inside another organism, but the term is
usually restricted to arrangements of mutual benefit, thus not
including parasite-host relationships. A number of eukaryotic
cell organelles (including mitochondria) are believed to have
originated from endosymbiotic relationships between eukaryotic
cells and simpler cells.
... ... *electron transport: See main report.
... ... *oxidative phosphorylation: Production of ATP during
aerobic respiration. It takes place in the mitochondria of
eukaryotic cells and requires molecular oxygen as a terminal
electron acceptor.
... ... *redox potentials: Chemical potentials in a chemical
reaction involving the simultaneous reduction and oxidation of
two compounds by a transfer of electrons between them.
... ... *chromatin: The entire complex of a eukaryotic
chromosome, including DNA, chromosomal proteins, and chromosomal
RNA.
... ... *membrane blebbing: Refers to the macroscopic blistering
of the surfaces of cells when they die under certain conditions.
-----------
ScienceWeek 22 Mar 2002 www.scienceweek.com
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
5. ON EUKARYOTIC DNA REPLICATION
David M. Gilbert (SUNY Upstate Medical University, US) discusses
DNA replication, the author making the following points:
1) Transmission of genetic information from one cell
generation to the next requires the accurate and complete
duplication of each DNA strand exactly once before each cell
division. Typically, this process begins with the binding of an
"initiator" protein to a specific DNA sequence or "replicator".
In response to the appropriate cellular signals, the initiator
directs a local unwinding of the DNA double helix and recruits
additional chemical entities ("factors") to initiate the process
of DNA replication.
2) The above paradigm describes most of the currently
tractable replication systems, and although derived from
prokaryotic and viral systems, there is no compelling reason to
doubt that it will apply to all eukaryotic organisms. In fact,
the proteins that regulate replication are highly conserved from
yeast to humans, including the "origin recognition complex",
which binds directly to replication origin sequences in budding
yeast. However, in several eukaryotic replication systems, it
appears that any DNA sequence can function as a replicator. Those
outside the field are often perplexed as to how investigators of
different eukaryotic systems can work with assumptions that range
from very specific to completely random origin sequence
recognition, yet all agree on the basic mechanism regulating DNA
replication.
3) The resolution may lie in a model for once-per-cell-cycle
regulation of eukaryotic replication that does not require
defined origin sequences. This model implies that the
specification of precise origins is a response to selective
pressures that transcend those of once-per-cell-cycle
replication, such as the coordination of replication with other
chromosomal functions. Viewed in this context, the locations of
origins may be an integral part of the functional organization of
eukaryotic chromosomes.
-----------
Science 2001 294:96
-----------
ScienceWeek 22 Mar 2002 www.scienceweek.com
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
6. ON THE ELUSIVE NEANDERTHALS
C. Stringer and W. Davies (Natural History Museum London, UK)
discuss the Neanderthals, the authors making the following
points:
1) The fate of the Neanderthals -- the distinctive humans
who occupied Europe immediately before the modern-looking Cro-
Magnons appeared -- remains unclear. We are still far from
pinning down the processes that caused the Neanderthals to vanish
approximately 30,000 years ago, after existing for at least
200,000 years before that.
2) Previous views on the question have ranged from a denial
that the Neanderthals disappeared at all (with a proposal that
the Neanderthals simply evolved into modern humans) to arguments
that they were killed off rapidly by invading and vastly superior
Cro-Magnons. At present, both DNA and morphological studies
support the majority view that the Neanderthals were indeed a
separate lineage, and probably a separate species, from modern
humans. But equally, there is growing evidence from dating
techniques that the Neanderthals did not vanish overnight, and
that in some ways they were as behaviorally sophisticated as the
Cro-Magnons.
3) Increased knowledge of the vagaries of Europe's climate
over the past 100,000 years is beginning to influence thinking
about Neanderthal extinction. Cores from the Greenland icecap and
the floor of the North Atlantic reveal remarkable oscillations in
temperatures during that time, dramatic fluctuations of climate
change that could have had severe effects on both Neanderthals
and Cro-Magnons, reducing the capacity of the environment to
support them. According to one view, Neanderthals became extinct
simply because they could not cope with the increasing severity
of climatic change approximately 30,000 years ago. The idea is
that the Cro-Magnons were better adapted to the increasing open-
country environments and simply colonized the vacant habitats. An
alternative view is that extinction probably stemmed from various
factors, including climatic instability coupled with competition
for resources from Cro-Magnons.
-----------
Nature 2001 413:791
-----------
ScienceWeek 22 Mar 2002 www.scienceweek.com
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
7. ON THE PERSISTENT RADICAL EFFECT IN CHEMICAL SYSTEMS
Hanns Fischer (University of Zurich, CH) discusses radicals in
chemical systems, the author making the following points:
1) Whenever in a chemical system transient and persistent
radicals are formed with equal or similar rates, be it from the
same or different precursors, their cross-reaction products are
produced with a surprisingly high selectivity, and the otherwise
prominent self-termination products of the transient radicals are
virtually absent. This is not because the self-termination
reaction does not take place at all. On the contrary, this
reaction, combined with the reluctance of persistent species to
undergo any self-termination, causes a build-up of a considerable
excess of the persistent over the transient species, and this
excess then steers the reaction system toward the cross-reaction
channel. Thus, the system orders itself in time, and although the
self-termination reaction of the transient radicals is important,
it causes its own suppression.
2) This is the basic principle of the "persistent radical
effect". There are many variants, since there are additional
reversible and irreversible reactions of the transient radicals,
but these do not alter the essentials. Although it is quite
natural, the principal seems paradoxical, and it not easily
accepted on first sight. It took a long time from its first
formulation in 1936, and several reinventions, until it is now
clearly recognized that it operates in diverse branches of
chemistry. As might be expected, the often high selectivity of
cross-reaction product formation in such systems appeals to
synthetic chemists.
-----------
Chem Revs. 2001 101:3581
-----------
ScienceWeek 22 Mar 2002 www.scienceweek.com
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
8. ON THE ENGINEERING OF SUPRAMOLECULAR CRYSTALS
T.L. Nguyen et al (State University of New York Stony Brook, US)
discuss supramolecular crystal engineering, the authors making
the following points:
1) Crystal engineering (in this context, supramolecular
synthesis) is an important problem that requires a detailed
knowledge of intermolecular interactions. One would like to be
able to choose appropriate molecules or sets of molecules and
predict with confidence the manner in which they will
crystallize. This is a difficult problem of great complexity, and
indeed in many cases there may be no simple thermodynamic basis
for a successful prediction. Crystallization is a kinetic
process, and polymorphism often appears when it is most
inconvenient. The authors suggest that chemists persevere with a
certain confidence that by a clever design they will achieve the
structural result they seek. Success is achieved either by wisely
setting limited structural goals in the first place, or by making
judicious use of ex post facto crystal design.
2) Despite these difficulties, one can still imagine a
scenario where one could reliably predict the total structure of
a crystal purely on the basis of knowledge of molecular
properties. Total structure prediction would require
specification of molecular geometry and orientation, unit cell
dimensions, and the space group. The authors report that their
simplified approach to this problem has been to identify
molecular functionalities that will predictably and persistently
lead to crystals containing defined network structures. Each
chosen functionality has a size and shape that leads to
characteristic repeat distances within its networks, and these
molecular networks are substructures of the final crystal. The
networks have repeat distances commensurate with the unit cell of
the crystal, and their group symmetries are a subgroup of the
space group of the final crystals. The distance parameters can be
predicted, and a consideration of molecular symmetry combined
with the symmetry of each anticipated intermolecular bond can
lead one to the correct network symmetry. The authors state: "By
combining good chemical insight with solid crystallographic
principles, one can design or engineer crystalline solids that
contain networks with desired structural features."
-----------
J. Am. Chem. Soc. 2001 123:11057
----------
Related Background:
SUPRAMOLECULAR CHEMISTRY
S.T. Nguyen et al (Northwestern University, US) discuss
supramolecular chemistry. For over 100 years, chemistry has
focused primarily on understanding the behavior of molecules and
their construction from constituent atoms, and our current level
of understanding of molecules and chemical construction
techniques has given us the confidence to tackle the construction
of virtually any molecule, be it biological or designed, organic
or inorganic, monomeric or macromolecular in origin. During the
last few decades, chemists have extended their investigations
beyond atomic and molecular chemistry into the realm of
"supramolecular chemistry". Terms such as "molecular self-
assembly", "hierarchical order", and "nanoscience" are often
associated with this area of research. In general, supramolecular
chemistry is the study of interactions between, rather than
within, molecules -- in other words, chemistry using molecules
rather than atoms as building blocks. Whereas traditional
chemistry deals with the construction of individual molecules (1
to 100 angstroms length scale) from atoms, supramolecular
chemistry deals with the construction of organized molecular
"arrays" with much larger length scales (1 to 100 nanometers). In
classical molecular chemistry, strong association forces such as
covalent and ionic bonds are used to assemble atoms into discrete
molecules and hold them together. In contrast, the forces used to
organize and hold together supramolecular assemblies are weaker
non-covalent interactions, such as hydrogen bonding, polar
attractions, van der Waals forces, and hydrophilic-hydrophobic
interactions.
-----------
Proc. Nat. Acad. Sci. 2001 98:11849
-----------
Related Background:
SUPRAMOLECULAR CHEMISTRY
Gautam R. Desiraju (University of Hyderabad, IN) discusses
supramolecular chemistry. For a long time, chemists have tried to
understand nature at a level purely molecular, considering only
structures and functions involving strong covalent bonds. But
some of the most important biological phenomena do not involve
the making and breaking of covalent bonds, the linkages that
connect atoms to form molecules, Instead, biological structures
are usually made from loose aggregates held together by weak non-
covalent interactions. Because of their dynamic nature, these
interactions are responsible for most of the processes occurring
in living systems. Chemists have been slow to recognize the
enormous variety -- in terms of structure, properties, and
functions -- offered by this more relaxed approach to making
chemical compounds. The slow shift toward this new approach began
in 1894, when Emil Fischer (1852-1919) proposed that an enzyme
interacts with its substrate as a key does with its lock. This
elegant mechanism contains the two main tenets of what would
become a new subject, supramolecular chemistry. These two
principles are molecular recognition and supramolecular function.
The term "supramolecular chemistry" was coined in 1969 by Jean-
Marie Lehn in his study of inclusion compounds and cryptands. The
award of the 1987 Nobel Prize in Chemistry to Charles Pedersen,
Donald Cram, and Lehn signified the formal arrival of the subject
on the chemical scene. Lehn defined supramolecular chemistry as
"the chemistry of the intermolecular bond". Just as molecules are
built by connecting atoms with covalent bonds, supramolecular
compounds are built by linking molecules with intermolecular
interactions.
-----------
Nature 2001 412:397
-----------
Related Background:
SUPRAMOLECULAR ASSEMBLIES: CURRENT AND FUTURE RESEARCH
One has the sense that a renaissance in materials science is
underway, a significant refocusing with a potential impact at
least as great as that following the introduction of plastics
more than a century ago. At a recent materials science symposium
on "Materials for the 21st Century and Beyond" (April 29, Hunter
College New York, US), seven leading figures in the field
presented perspectives on the near future. Nobel Laureate Jean-
Marie Lehn (Louis Pasteur University Strasbourg, FR) reviewed the
work of his group in designing and creating molecules programmed
by virtue of their structure and functional groups to
spontaneously organize themselves into larger supramolecular
assemblies held together by hydrogen bonds, metal coordination,
and so on. The interest is not so much in the mere self-assembly
into large structures, but in the fact that such self-assembled
structures exhibit a new spectrum of physical and chemical
properties with important potential practical applications.
Lehn's research involves the use of metal ions to organize and
stabilize supramolecular structures with reversible
architectures, and such structures have special redox, optical,
magnetic and other properties. Michael D. Ward (University of
Minnesota Minneapolis, US) reported on the use of molecular
building blocks to construct crystalline frameworks with
preordained architectures and new functions. Ward's structures
involve sheets of organic cations and organic anions
hydrogen-bonded to each other in a hexagonal arrays. Work by
other groups has involved supramolecular multilayers. In 1988,
researchers discovered that when certain films consisting of
alternating layers of a magnetic and a non-magnetic metal are
placed in a magnetic field, the resistance of the film changes
markedly, a phenomenon known as "giant magnetoresistance". This
discovery apparently reenergized the magnetic materials science
field because of important possible applications to information
storage technology, and Stuart P. Parkin (IBM San Jose, US) is
now leading a productive research group in this field. Ron Dagani
(Chemical and Engineering News), who authors a review of the
symposium, concludes: "Parkin's lecture made it clear that, at
least in the case of magnetic multilayers, some materials
envisioned for the 21st century are already here."
-----------
Chem. & Eng. News 8 Jun 98
-----------
ScienceWeek 22 Mar 2002 www.scienceweek.com
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
9. CHARGE TRANSFER AND THE ISOMER EFFECT
T. Kusakabe et al (Kinki University, JP) discuss charge transfer,
the authors making the following points:
1) The understanding of charge transfer processes in
collisions of ions and hydrocarbons above intermediate collision
energies has been extremely limited due to the complexity of the
target. Such understanding, however, is becoming more and more
important in various applications in plasma, material, medical,
and astrophysical science. In research concerning controlled
thermonuclear fusion, these collisions play a key role in low
temperature edge plasmas of current fusion devices with carbon-
coated or graphite-lined walls as plasma-facing materials. In
addition, these collisions are critical in understanding various
important features in high-tech applications such as plasma-based
material production. Finally, such collision processes obviously
constitute an important part of astrochemistry.
2) For hydrocarbon molecules, as the number of carbon atoms
increases, in general the number of isomers increases. The
C(sub3)H(sub4) is known to possess two stable isometric-molecular
structures, allene (propadiene) and propyne (methylacetylene). It
is known that isomers always show conspicuous differences in
various physical and chemical properties in stationary or
dynamical aspects in the interaction energy equivalent to the
thermal energy domain. And indeed, strong isomer effects have
recently been observed in total and differential elastic cross
sections for C(sub3)H(sub4) isomers, and were observed earlier in
other systems in electron impact experiments. However, as a
natural consensus, it has been believed that the isomer effect
would quickly disappear as the energy increased above a few tens
of electron-volts because of a shorter interaction time, and the
question has thus been entirely ignored in past experimental
studies.
3) The authors report they have observed, for the first
time, prominent isomer effects in charge-transfer processes in
collision of C(+) ions with allene and propyne even at collision
energies as high as a few hundred electron-volts. The authors
report the present charge transfer cross sections for allene are
found to be systematically larger than those for propyne in the
entire energy range studied (up to 4.5 keV).
-----------
Phys. Rev. Lett. 2001 87:243201
-----------
ScienceWeek 22 Mar 2002 www.scienceweek.com
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
10. BIOPHYSICS: OSCILLATING PROTEINS AND BACTERIAL CELL DIVISION
In general, in theoretical chemistry, a "reaction-diffusion
system" involves the coupling between a chemical reaction and
molecular diffusion, with the coupling modifying the rate of the
reaction. In a reaction-diffusion system, according to theory,
nonlinear dynamic processes may result in the appearance of
density fluctuations. One important aspect of such systems is
that the theoretical nonlinear equations that describe them are
not "well-behaved": solutions to the equations can be extremely
sensitive to small perturbations. For example, I. Prigogine and
his co-workers demonstrated theoretically 20 years ago that in a
reaction-diffusion system, the interaction of density
fluctuations with gravity results in a small directional
transport term in the equation describing the system, a term that
can destabilize the equilibrium state and push the system into
the formation of macroscopic patterns.
... ... M. Howard et al (Simon Fraser University, CA) discuss
oscillating proteins, the authors making the following points:
1) The subcellular spatial and temporal organization of
bacterial proteins is largely unknown, although the spatial
distribution of proteins on the cytoplasmic membrane of bacteria
are known to be important for chemotaxis and for DNA replication.
Understanding how the supramolecular organization of proteins
affects bacterial function represents a considerable experimental
and theoretical challenge.
2) In contrast to nucleated eukaryotic cells, no large
organelles are present in the bacterial interior (cytoplasm), and
no active transport mechanisms such as molecular motors are known
to function in these systems. However, recent video microscopy of
fluorescence-labeled proteins involved in the regulation of
division of the bacterium E. coli have uncovered coherent and
stable spatial and temporal oscillations in three proteins: MinC,
MinD, and MinE. These proteins apparently oscillate from end to
end of the bacterium and move between the cytoplasmic membrane
and the cytoplasm. These min-proteins select the site for the
next bacterial division. Despite a wealth of phenomenological
detail, no quantitative models have been developed to explain how
the min-proteins organize into oscillating structures.
3) The authors focus on E. coli, a commonly studied rod-
shaped bacterium, approximately 2 to 6 microns in length and
approximately 1 to 1.5 microns in diameter. Each E. coli divides
approximately every hour, depending on the conditions -- first
replicating its DNA, then dividing in half to form two viable
daughter cells. The MinCDE oscillations are known to persist even
when protein synthesis is suppressed; DNA replication and
septation occur even without the min-proteins.
4) The authors present a reaction-diffusion model describing
the diffusion of min-proteins along the bacterium and their
transfer between the cytoplasmic membrane and cytoplasm. The
model spontaneously generates protein oscillations in good
agreement with experiments. The authors explore the oscillation
stability, frequency, and wavelength as a function of protein
concentration and bacterial length.
-----------
Phys. Rev. Lett. 2001 87:278102
-----------
ScienceWeek 22 Mar 2002 www.scienceweek.com
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
11. PHYSICAL CHEMISTRY: THE GLASS TRANSITION OF WATER
Dennis D. Klug (National Research Council, CA) discusses phase
transitions of water, the author making the following points:
1) Few known simple molecular systems can rival the
complexity of the water phase diagram. Water boasts numerous
solid phases and may even form two different liquid phases at low
temperatures. But pinning down the exact nature of the different
phases and the transitions between them has proved difficult.
2) One of the intractable properties of water is the
temperature at which water changes from a liquid to a glassy
state. The glass transition temperature is usually defined as the
temperature at which the liquid becomes very viscous and
essentially a quenched liquid upon cooling, or as the temperature
at which the solid-like glass transforms to a liquid upon
heating. This is an operational rather than a thermodynamic
definition, because the glass transition temperature depends, for
example, on the rate at which the liquid is cooled. On timescales
of a picosecond, even liquid water at room temperature is quite
hard.
3) Experimental studies of the liquid and amorphous phases
of water indicate a highly complex behavior. Several theories
suggest the possible existence of two distinct liquid water
phases, a liquid-liquid phase transition upon cooling, and a
liquid-liquid critical point in the low-temperature region of the
phase diagram. The glass transition may occur in one of these
liquid forms of water if the theories are correct. The location
of the glass transition defines the region where one can search
for the low-temperature liquid, the liquid-liquid transition, and
the proposed second critical point. The glass transition of water
is also of interest in the context of cryoprotection processes
and biological organisms at low temperature.
-----------
Science 2001 294:2305
-----------
ScienceWeek 22 Mar 2002 www.scienceweek.com
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
12. VIBRATIONAL CONTROL IN CHEMICAL REACTIONS
Z.H. Kim et al (Stanford University, US) discuss vibrational
control of chemical reactions, the authors making the following
points:
1) Driving a chemical reaction to a specific desired product
continues to be central theme of chemistry. If we picture a
chemical reaction as the transformation from reagents to specific
products along a minimum energy path called the "reaction
coordinate", an intuitive way of driving the reaction to a
desired product is to excite one of the reagents so that its
internal motion is along the reaction coordinate. Depending on
the nature of the transition state, the vibrational mode of a
reagent along the reaction coordinate can be as simple as a bond
stretch of one of the reagents or it can be as complex as the
collective motion of the overall reagent.
2) By studying the effect of vibrational excitation on the
chemical reaction, we not only test the concept of vibrational
control, but also learn how the reaction takes place. To date,
only a few experimental realizations of vibrational control of
simple chemical reactions have been achieved. The first example
of controlling a reaction in which different vibrational motions
of the reagents are excited is H + HOD. These studies
demonstrated that vibrational excitation of the OH bond in HOD
leads almost exclusively to the H(sub2) + OD product channel,
whereas the excitation of OD stretching produces the HD + OH
products. Similar results were reported for Cl + HOD. These
results indicate that the unexcited part of the molecule acts
merely as a "spectator", playing no role in influencing the
outcome of the reaction. The effectiveness of vibrationally
controlled chemistry as applied to reactions involving larger and
more complex molecules remains an unsettled issue.
-----------
J. Am. Chem. Soc. 2001 123:12714
-----------
ScienceWeek 22 Mar 2002 www.scienceweek.com
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
13. USE OF BACTERIA IN THERAPY AGAINST TUMORS
R.K. Jain and N.S. Forbes (Harvard University, US) discuss
bacteria and cancer therapy, the authors making the following
points:
1) Hypoxia and anoxia are pathophysiologic characteristics
of most solid tumors. For nearly 150 years, non-pathogenic
anaerobic bacteria that preferentially localize and proliferate
in the hypoxic regions of tumors have been investigated as
treatments for experimental and human tumors with mixed success.
In recent years, there has been a renewed interest in using such
bacteria as innovative delivery vehicles for gene therapy.
2) In tumors, blood vessels are structurally and
functionally abnormal, resulting in temporally and spatially
heterogeneous blood flow. This heterogeneity hinders the delivery
of blood-borne therapeutics to all cancer cells and leads to
acutely and/or chronically hypoxic and acidic regions in tumors.
These conditions reduce the effectiveness of radiation and some
chemotherapeutic agents and select for cancer cells that are more
aggressive, metastatic, and resistant to various therapies.
3) Ironically, the metabolically comprised environment of a
tumor provides a haven for a number of anaerobic bacteria, and
indeed over the past 50 years several strains of facultative and
obligate anaerobic bacteria have been shown to localize and cause
destruction of cancer cells by lysis in transplanted tumors in
animals. These initial animal studies were so encouraging that
clinical trials using Clostridium began in the 1960s.
Unfortunately, the results were not as impressive as anticipated
and the trials were discontinued. Now, with the advent of genetic
engineering of bacteria, there is hope that specific species of
bacteria may be genetically engineered to serve as useful
vehicles for gene therapy against tumors.
-----------
Proc. Nat. Acad. Sci. 2001 98:14748
-----------
ScienceWeek 22 Mar 2002 www.scienceweek.com
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
14. ON GENETIC DIVERSITY AND DISEASE
John M. Scott (Trinity College Dublin, IE) discusses genetic
diversity and disease, the author making the following points:
1) Historically, the investigation of nature's mistakes in
the form of so-called "inborn errors of metabolism" has attracted
wide and justifiable interest. Some of these errors, such as
phenylketonuria, are important in their own right; although rare,
they are treatable and thus of considerable public health
interest. Others, although less common and less treatable, such
as the inborn errors that affect cobalamin (Vitamin B-12)
metabolism are important because they provide an insight into the
role of an enzyme or biochemical pathway in the maintenance of
normal function and health.
2) It is obvious, however, that these historical examples do
not include a whole aspect of genetic variation and disease that
remains largely uninvestigated. Epidemiological studies indicate
that there is a very significant familial component to virtually
all chronic diseases such as cardiovascular disease, colorectal
cancer, or common birth defects such as spina bifida and other
neural tube defects. As the human genome is sequenced,
researchers find that although certain sequences are highly
conserved, even within these conserved sequences there are some
genetic variations: insertions, deletions, and (more frequently)
single nucleotide polymorphisms. The mapping of the human genome
has now presented the opportunity to identify within a very short
period all the common genetic polymorphisms, and the challenge
will be to determine whether these result in an altered phenotype
and whether this alteration in phenotype in turn results in
increased risk of a particular disease.
-----------
Proc. Nat. Acad. Sci. 2001 98:14754
-----------
ScienceWeek 22 Mar 2002 www.scienceweek.com
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
15. EFFECTS OF MATERNAL CIGARETTE SMOKING
X. Wang et al (Boston University, US) discuss the effects of
maternal cigarette smoking, the authors making the following
points:
1) In the US, 65 percent of all infant deaths occur among
low-birth-weight infants (less than 2500 grams), with such
infants accounting for 7.6 percent of all live-born infants. The
etiology of low birth weight is largely unknown, but both
environmental and genetic factors may play a role. Numerous
studies have demonstrated that maternal cigarette smoking during
pregnancy is associated with reduced birth weight or increased
risk of low birth weight.
2) In 1997, 13.2 percent of US women reported smoking
cigarettes during pregnancy. Maternal cigarette smoking is
identified as the single largest modifiable risk factor for
intrauterine growth restriction in developed countries. However,
not all women who smoke cigarettes during pregnancy have low-
birth-weight infants. The reason for this variability is largely
unknown, but may be related to maternal genetic susceptibility.
3) Tobacco smoke contains approximately 4000 compounds. The
most important carcinogens in tobacco smoke are polycyclic
aromatic hydrocarbons, arylamines, and N-nitrosamines. The
ability of an individual to convert toxic metabolites of
cigarette smoke to less harmful moieties is important for
minimizing the adverse health effects of these compounds. Using
polycyclic aromatic hydrocarbons (PAHs) as an example, the
metabolic processing of these compounds in humans involves 2
phases: a) an activation process, in which the inhaled
hydrophobic PAHs are converted mainly via aryl hydrocarbon
hydroxylase activity into hydrophilic reactive electrophilic
intermediates that can bind covalently to macromolecules,
especially to DNA. These intermediates may be more toxic than the
original form; b) a detoxification process, in which these
metabolic intermediates are detoxified by enzymes via
transformation into conjugate forms sufficiently polar to be
excreted from the body.
4) The authors investigated the correlation between
polymorphisms of 2 metabolic genes (CYP1A1 and GSTT1) and the
relation between maternal cigarette smoking and infant birth
weight. 741 human mothers were involved in the study. The authors
report that maternal CYP1A1 and GSTT1 genotypes modified the
association between maternal cigarette smoking and infant birth
weight, indicating an interaction between metabolic genes and
cigarette smoking.
-----------
J. Am. Med. Assoc. 2002 287:195
----------
Related Background:
MEDICAL BIOLOGY: SMOKING PREVALENCE AMONG ADULTS IN THE US 1998
One of the ironies of contemporary society is that toxic
chemicals that enter the body through the digestive tract are
more tightly regulated by governments than toxic chemicals that
enter the body through the lungs. If the plant called "lettuce"
were found to cause millions of cases of cancer, stroke, heart
disease, and lung disease, lettuce would quickly vanish as a
marketable commodity, no matter how many lettuce growers squealed
in protest. But the plant tobacco, which does cause millions of
cases of cancer, stroke, heart disease, and lung disease, is not
only still a marketable commodity in the US, but more young
people than ever in the US, and more people worldwide, are
smoking cigarettes. In the US, a contagious disease that caused
as many deaths as cigarette-selling would be called a plague;
instead, in the US, cigarette-selling is called an "industry".
Well, if it is an industry, it's an industry devoted to the sale
of an addictive lethal drug, a drug no less lethal because it
kills people in 20 or more years rather than killing people
immediately.
... ... The US Centers for Disease Control and Prevention (CDC)
presents the results of a 1998 survey administered to a
nationally representative sample (n = 32,440) of the US non-
institutionalized civilian population aged >= 18 years. The
report makes the following points:
1) Participants were asked, "Have you smoked at least 100
cigarettes in your entire life? and "Do you now smoke cigarettes
every day, some days, or not at al?" "Current smokers" were
defined as persons who reported both having smoked greater than
or equal to 100 cigarettes during their lifetime and having
smoked every day or some days at the time of the interview.
"Former smokers" were defined as those who had smoked >= 100
cigarettes during their lifetime but did not currently smoke.
2) In 1998 in the US, an estimated 47.2 million adults (24.1
percent of the adult population), comprising 24.8 million men
(26.4 percent) and 22.4 million women (22.0 percent) were current
smokers. Overall, 19.7 percent of adults were every day smokers,
and 4.2 percent were some day smokers. Every day smokers
constituted 82.4 percent of all smokers.
3) Prevalence of smoking was highest among persons aged 18
to 24 years (27.9 percent) and aged 25 to 44 years (27.5
percent), and lowest among persons aged >= 65 years (10.9
percent).
4) Among specific groups, prevalence of current smoking was
as follows:
... ... American Indians/Alaska Natives: 40 percent
... ... Non-Hispanic whites: 25 percent
... ... Non-Hispanic blacks: 24.7 percent
... ... Hispanics: 19.1 percent
... ... Asian/Pacific Islanders: 13.7 percent
5) Current smoking prevalence was lowest among persons with
at least 16 years of education (11.3 percent) and highest among
persons with 9 to 11 years of education (36.8 percent). Smoking
prevalence was higher among persons living below the poverty
level (32.3 percent) than among those living at or above the
poverty level (23.5 percent).
6) In 1998, an estimated 44.8 million adults (22.9 percent
of the adult population) were former smokers (25.7 million men
and 19.1 million women). Former smokers constituted 48.7 percent
of persons who had ever smoked >= 100 cigarettes. Among current
daily smokers in 1998, an estimated 15.2 million (39.2 percent)
had stopped smoking for at least 1 day during the preceding 12
months because they were trying to stop smoking.
7) The report concludes: "A comprehensive approach to
tobacco control will require treatment for nicotine dependence
and efforts at national, state, and local levels to reduce youth
smoking, promote smoke-free environments, support
countermarketing efforts, and eliminate disparities in tobacco
use among population subgroups. Increased attention must be
focused on groups that show no decline in smoking prevalence,
including persons aged 18 to 24 years, adults with low education
levels, and American Indians/Alaska Natives. Approaches with the
widest scope (i.e., economic, regulatory, and comprehensive) are
likely to have the greatest long-term population impact."
-----------
CDC Morbidity and Mortality Weekly Report 2000 49:881
J. Amer. Med. Assoc. 2000 284:2180
-----------
Related Background:
ON EDUCATING PHYSICIANS CONCERNING TOBACCO DEPENDENCE
Tobacco use is the leading cause of preventable death and
disability in the US, accounting for nearly 500,000 premature
deaths per year. Although 70 percent of smokers visit a physician
each year, most patients are not advised or assisted in an
attempt to quit smoking. A 1991 survey indicated that only 21
percent of practicing physicians felt their formal medical
training prepared them to help patients stop smoking.
... ... L.H. Ferry et al (3 authors at Loma Linda University, US)
now present the results of a survey designed to assess the
content and extent of tobacco curricula in US undergraduate
medical education. In this context, the phrase "tobacco
curricula" includes epidemiology of tobacco use, prevention, risk
of tobacco-related diseases, and tobacco dependence treatment.
The phrase "smoking cessation" includes behavior modification
techniques, pharmacotherapy, and counseling skills. The authors
received data from 122 US medical schools (98.6 percent of the
total medical schools in the US). The authors report that a
majority of US medical school graduates are not adequately
trained to treat nicotine dependence. The authors suggest that
the major deficit is the lack of smoking cessation instruction
and evaluation in the clinical years of medical training, and
that a model core tobacco curricula that meets national
recommendations should be developed and implemented in all US
medical schools. The authors conclude: "Until all medical schools
place sufficient emphasis on the knowledge base and intervention
skills needed to prevent and treat chronic tobacco-related
diseases, it is unlikely we will see a decline in tobacco-related
morbidity and mortality. However, if medical schools provide
universal training of medical students in nicotine dependence
intervention, tobacco users will have access to the professional
expertise they need to end the deadly cycle of nicotine
addiction."
-----------
J. Amer. Med. Assoc. 1999 282:825
-----------
Related Background:
ON THE TOBACCO INDUSTRY AND NICOTINE AS AN ADDICTIVE DRUG
In 1994 the state of Minnesota filed suit against the tobacco
industry, and although this trial is now history, there are many
people who feel the legacy of the trial will carry on into the
21st century because of the revelations contained in the millions
of pages of previously secret internal tobacco industry documents
made public in the trial. ... ... R.D. Hurt and C.R. Robertson
now present an extensive review of the material in a medical
journal from the perspective of medical science, and the authors
make the following points: 1) The litigation tobacco industry
documents reveal that for decades the tobacco industry knew and
internally acknowledged that *nicotine is an addictive drug and
that cigarettes are the ultimate nicotine delivery device. The
following statements by executives, for example, are found in
tobacco industry documents: "Very few consumers are aware of the
effects of nicotine, i.e., its addictive nature and that nicotine
is a poison." (H.D. Steele, Brown and Williamson Tobacco Company,
1978). And in another Brown and Williamson memo: "Nicotine is the
addicting agent in cigarettes." (A.J. Mellman, Brown and
Williamson Tobacco Company, 1983). Concerning cigarettes as a
drug delivery device, the litigation documents reveal that C.E.
Teague Jr., assistant director of research at R.J. Reynolds
Tobacco Company, wrote in 1972 in an internal memorandum: "In a
sense, the tobacco industry may be thought of as being a
specialized, highly ritualized and stylized segment of the
pharmaceutical industry. Tobacco products, uniquely, contain and
deliver nicotine, a potent drug with a variety of physiological
effects... Thus a tobacco product is, in essence, a vehicle for
delivery of nicotine." 2) The authors report that perhaps their
most surprising finding in the document review was the evidence
of tobacco industry efforts spanning 3 decades to alter the
chemical form of nicotine to increase the percentage of freebase
nicotine delivered to smokers. Depending on pH, nicotine exists
as a diprotonated salt, a monoprotonated salt, or an uncharged
neutral species. The salt forms are called the "bound" forms, and
the neutral species is called the "freebase" form. Nicotine
favors the salt form at low values of pH (e.g., pH = 3) and the
freebase form at high values of pH (e.g., pH = 8). Freebase
nicotine apparently crosses biological membranes more easily than
the charged counterparts, and this affects the physiological
response to the drug. The tobacco industry was apparently well
aware of these properties of nicotine as far back as 1966, and
for 3 decades the tobacco industry had a focus on developing high
pH delivery of nicotine to increase its physiological effects.
The authors conclude: "When the breadth and depth of tobacco
industry actions are understood, it becomes evident that allowing
a tobacco settlement that honors the industry demands for legal
and financial immunity would be a public health disaster of epic
proportions and would allow the industry to continue to promote
its deadly product throughout the 21st century. Congress must use
its power to stop the carnage of more than 400,000 Americans
dying each year of cigarette-related diseases."
-----------
J. Amer. Med. Assoc. 1998 280:1173
-----------
Notes:
... ... *nicotine: The alkaloid nicotine
[3-(1-methyl-pyrrolidyl)pyridine] is a tertiary amine composed of
pyridine and pyrrolidine rings. The current consensus among
neuropharmacologists is that nicotine is the psychoactive drug
primarily responsible for the addictive nature of tobacco use.
Nicotine is highly selective for so-called "nicotinic receptors"
for *acetylcholine in the peripheral and central nervous systems,
and activation of these receptors is the likely source of the
psychoactive effects of the drug. The nicotinic-acetylcholine
receptor is a molecularly well-characterized receptor, and its
activation evidently leads to conformation changes in its 5
subunits that result in a transient increase of permeability of
the neuron membrane to the sodium ion. The nicotinic-
acetylcholine receptor is therefore characterized as a
neurotransmitter-gated ion channel. Concentrations of nicotine in
blood rise quickly during cigarette smoking and peak at its
completion. Nicotine is also deposited in the lungs, spleen,
liver, and brain, where concentrations are typically twice those
of measurable blood concentrations. Nicotine readily crosses the
*blood-brain barrier, leading to the release of acetylcholine,
*norepinephrine, *dopamine, *serotonin, *vasopressin, *growth
hormone, *cortisol, *prolactin, *neurophysin 1, and
*adrenocorticotropic hormone, and release of these substances
causes various neuropharmacological effects. Apart from the
neuropharmacological effects of nicotine, nicotine and other
constituents in cigarette smoke elevate blood pressure, cause
*tachycardia, *arrhythmia, and *vasoconstriction in *cutaneous
tissue and skin; lower body temperature; inhibit *diuresis;
increase *gastrointestinal tonus; antagonize ulcer healing; and
decrease pain threshold.
... ... *acetylcholine: A prevalent *neurotransmitter substance,
both in the brain and in the peripheral nervous system, where it
controls the actions of skeletal and smooth muscle.
... ... *neurotransmitter substance: Neurotransmitters are
chemical substances released at the terminals of nerve axons in
response to the propagation of an impulse to the end of that
axon. The neurotransmitter substance diffuses into the synapse,
the junction between the presynaptic nerve ending and the
postsynaptic neuron, and at the membrane of the postsynaptic
neuron the transmitter substance interacts with a receptor.
Depending on the type of receptor, the result may be an
excitatory or an inhibitory effect on the postsynaptic nerve
cell.
... ... *blood-brain barrier: A selective mechanism opposing the
passage of most ions and large molecular-weight compounds from
the blood to brain tissue, the mechanism operating in a
continuous layer of endothelial cells connected by tight
junctions between cells. (Endothelial cells are flat cells
forming a layer lining blood vessels, lymphatic vessels, the
heart, etc.)
... ... *norepinephrine: The principal neurotransmitter substance
released from nerve endings of the sympathetic nervous system.
(The sympathetic nervous system is a part of the autonomic
nervous system involved in the mobilization of energy resources
during stress and arousal.
... ... *dopamine: A neurotransmitter substance.
... ... *serotonin: A neurotransmitter substance involved in
nearly everything occurring in the brain, including psychological
states such as anxiety and depression, and dysfunctions producing
migraine and epilepsy.
... ... *vasopressin: A peptide hormone important in the
regulation of *diuresis.
... ... *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.
... ... *cortisol: A corticosteroid hormone secreted by the
adrenal gland.
... ... *prolactin: A polypeptide hormone synthesized and
released by the pituitary gland.
... ... *neurophysin 1: Neurophysins are a family of proteins
synthesized in the hypothalamus, and function as carriers in the
transport and storage of a number of hypothalamic-pituitary
hormones.
... ... *adrenocorticotropic hormone: (ACTH) A pituitary hormone.
... ... *tachycardia: Rapid beating of the heart, conventionally
applied to rates over 100 per minute.
... ... *arrhythmia: Irregularity of the heartbeat.
... ... *vasoconstriction: Narrowing of the blood vessels.
... ... *cutaneous tissue: In general, tissue associated with
skin.
... ... *diuresis: Excretion of large volumes of urine.
... ... *gastrointestinal tonus: In general, contraction of
gastrointestinal muscle.
-----------
Related Background:
EFFECTS OF NICOTINE ON BRAIN NERVE CELLS
... Dopamine is a neurotransmitter found in several major areas
of the brain, and the degeneration of so-called dopamine neurons
is apparently involved in Parkinson's disease. Dopamine has also
been implicated in the intricate effects of the psychostimulating
drugs associated with drug abuse. The dietary precursors of
dopamine are phenylalanine and l-tyrosine. The mesolimbic
dopamine system is a dopamine-involved system of nerve cells and
nerve fibers connecting the mesencephalon (the midbrain) to the
limbic system and cerebral cortex.
... ... Pidoplichko et al (4 authors at 2 installations, US)
report that the same concentration of nicotine achieved by
smokers activates and desensitizes multiple nicotinic receptors
with a resultant regulation of the activity of dopamine neurons.
The authors suggest these results further support the hypothesis
that the mesolimbic dopamine system is involved in the cellular
and behavioral effects of many addictive drugs.
-----------
Nature 1997 27 Nov 97
-----------
Related Background:
SECOND-HAND TOBACCO SMOKE DOUBLES RISK OF CORONARY PATHOLOGY
The most significant public health news of the week was probably
the report of a 10 year study by Ichiro Kawachi and colleagues
(Harvard School of Public Health, Cambridge MA US), which
tracked more than 32,000 healthy women who never smoked and
found that regular exposure to the smoke of other people at home
or work almost doubled the risk of heart disease. These new
findings are the largest increase in risk ever reported for
second-hand smoke, and the researchers state the findings apply
equally to men and women.
-----------
Circulation 1997 20 May 97
-----------
Related Background:
IN BRIEF: BIDI USE AMONG US URBAN YOUTH 1999
"Bidis" are small brown hand-rolled cigarettes primarily made in
India and southeast Asian countries, and consisting of tobacco
wrapped in a tendu or temburni leaf (Diospyros melanoxylon). In
the US, bidis are purchased for $1.50 to $4.00 for one package of
20 and are available in different flavors (e.g., cherry,
chocolate, and mango). Bidi use was first observed in the US
during the mid-1990s and is apparently now widespread among
various minority youth groups. Adolescents report a preference
for the taste of bidis over cigarettes and a belief that bidis
are less expensive, easier to buy, and safer than cigarettes. The
US Centers for Disease Control and Prevention (CDC) recently
presented a report on bidi use, the report making the following
points:
1) Preliminary data collected from a sample of adolescents
surveyed during March and early April 1999 in Massachusetts (US)
on the prevalence of bidi use among urban youth indicate that of
642 youth surveyed, 40 percent had smoked bidis at least once
during their lifetimes and 16 percent were current bidi smokers.
2) When tested on a standard smoking machine, bidis produced
higher levels of carbon monoxide, nicotine, and tar than
cigarettes, with one study reporting that bidis produced
approximately 3 times the amount of carbon monoxide and nicotine
and approximately five times the amount of tar as cigarettes.
Because of low combustibility of the tendu leaf wrapper, bidi
smokers inhale more often and more deeply, breathing in greater
quantities of tar and other toxins than cigarette smokers. Like
all tobacco products, bidis are mutagenic and carcinogenic. Bidi
smokers risk coronary heart disease, cancers of the oral cavity,
pharynx, larynx, lung, esophagus, stomach, and liver. Mortality
of both the fetus and newborn infant is also associated with bidi
use during pregnancy.
3) The report states that this investigation is the first in
the US to estimate the prevalence of bidi smoking among students
in grades 7 through 12, and that preliminary findings from this
study support the need for additional research on bidis,
particularly on smoking prevalence among youth from differing
geographic, educational, and socioeconomic backgrounds.
-----------
CDC Morbidity and Mortality Weekly Report 1999 48:796
J. Amer. Med. Assoc. 1999 282:1416
-----------
ScienceWeek 22 Mar 2002 www.scienceweek.com
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
16. HEALTH CARE AND RURAL AMERICA
S.J. Blumenthal and J. Kagen (Department of Health and Human
Services, US) discuss health care in rural US, the authors making
the following points:
1) Poverty, a major risk factor for poor health outcomes, is
more prevalent in inner-city and rural areas than in suburban
areas. In 1999, 14.3 percent of rural Americans lived in poverty
compared to 11.2 percent of urban Americans. Irrespective of
where they live, persons with lower incomes and less education
are more likely to report unmet health needs, less likely to have
health insurance coverage, and less likely to receive preventive
health care. When combined, these variables raise the risk of
death across all demographic populations.
2) Many of the ills associated with poverty, including lower
total household income and a higher number of uninsured
residents, are magnified in rural areas. In addition, rural
communities have fewer hospital beds, physicians, nurses, and
specialists per capita as compared to urban residents, as well as
increased transportation barriers to access health care.
3) The highest death rates for children and young adults are
found in the most rural counties, and rural residents see
physicians less often and usually later in the course of an
illness. People in rural America experience higher rates of
chronic disease and the health-damaging behaviors associated with
them. They are more likely to smoke, to lose teeth, and to
experience limitations from chronic health conditions. While
death rates from homicides are greater in urban areas, mortality
rates from unintentional injuries and motor vehicle crashes are
disproportionately more common in rural America.
-----------
J. Am. Med. Assoc. 2002 287:109
-----------
ScienceWeek 22 Mar 2002 www.scienceweek.com
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
17. DIABETES AND MICROVASCULAR PATHOLOGY
Michael Brownlee (Albert Einstein College of Medicine, US)
discusses diabetes, the author making the following points:
1) Diabetes-specific microvascular disease in the retina,
glomerulus of the kidney, and the blood vessels supplying nerves
(vasa nervorum) has similar pathophysiological features. Early in
the course of diabetes, intracellular hyperglycemia causes
abnormalities in blood flow and increased vascular permeability.
This reflects increased activity of vasodilators such as nitric
oxide, increased activity of vasoconstrictors such as angiotensin
II and endothelin-I, and elaboration of permeability factors such
as vascular endothelial growth factor. Quantitative and
qualitative abnormalities of extracellular matrix contribute to
an irreversible increase in vascular permeability.
2) With time, microvascular cell loss occurs, in part as a
result of programmed cell death, and there is progressive
capillary occlusion due both to extracellular matrix
overproduction induced by growth factors such as transforming
growth factor-beta (TGF-beta), and to deposition of periodic
acid-Schiff positive plasma proteins passing out of blood vessels
into surrounding tissues (extravasation). Hyperglycemia may also
decrease production of trophic factors for endothelial and
neuronal cells. Together, these changes lead to edema, ischemia,
and hypoxia-induced neovascularization in the retina,
proteinuria, kidney mesangeal matrix expansion, and
glomerulosclerosis in the kidney, and multifocal axonal
degeneration in peripheral nerves. In addition, diabetes-
accelerated atherosclerosis leads to increased risk of myocardial
infarction, stroke, and the necessity for limb amputation.
-----------
Nature 2001 414:813
-----------
ScienceWeek 22 Mar 2002 www.scienceweek.com
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
18. ON THE PREVALENCE OF CELIAC SPRUE
R.J. Farrell and C.P. Kelly (Harvard University, US) discuss
celiac sprue, the authors making the following points:
1) Celiac sprue, also known as celiac disease and gluten-
sensitive enteropathy, is characterized by malabsorption
resulting from inflammatory injury to the mucosa of the small
intestine after the ingestion of wheat gluten or related rye and
barley proteins. There is a clinical and histologic improvement
on a strict gluten-free diet, and relapse when dietary gluten is
reintroduced. The disorder results from inappropriate T-cell-
mediated immune response against ingested gluten in genetically
predisposed individuals.
2) Accounts of celiac sprue date back to the 1st century AD.
It was not until the 1940s, however, that the link to gluten
ingestion was established: Dicke, a Dutch pediatrician, observed
that the condition of children with celiac sprue improved during
the food shortages of World War II, only to relapse after cereal
supplies were restored.
3) Until fairly recently, celiac sprue was considered
uncommon in the US, with an estimated prevalence of 1 per 3000
population. But greater awareness of its presentations and the
availability of new and accurate serologic tests have led to the
realization that celiac sprue is relatively common, affecting 1
of every 120 to 300 persons in both Europe and North America.
4) The true prevalence of celiac sprue is difficult to
ascertain, because many patients have atypical symptoms or none
at all. A large multicenter Italian study identified 7 new cases
of celiac sprue in children for each patient with established
disease. The highest reported prevalence is in western Europe and
in places where Europeans emigrated, notably North America and
Australia. Celiac sprue is also found in parts of northwest
India, and it may be underdiagnosed in South America, North
Africa, and Asia. The disease is rare among people from a purely
African-Caribbean, Chinese, or Japanese background. In most
populations, there is a slight female preponderance in prevalence
of the disease.
-----------
New Engl. J. Med. 2002 346:180
-----------
ScienceWeek 22 Mar 2002 www.scienceweek.com
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
19. GLOBAL WARMING, SEA-LEVEL RISE, AND LOSS OF COASTAL WETLANDS
J.P. Donnelly and M.D. Bertness (Brown University, US) discuss
sea-level rise and coastal wetlands, the authors making the
following points:
1) Recent studies indicate that both climate warming and
increases in the rate of sea-level rise in New England over the
last 150 years are unprecedented in at least the last 1000 years.
The possibility that emission of greenhouse gases is influencing
and will continue to influence global climate and potentially
sea-level rise has prompted considerable research into the
possible implications for plant and animal communities.
2) The distribution of New England salt marsh communities is
intrinsically linked to the magnitude, frequency, and duration of
tidal inundation. Cordgrass (Spartina alterniflora) exclusively
inhabits the frequently flooded lower elevations, whereas a
mosaic of marsh hay (Spartina patens), spike grass (Distichlis
spicata), and black rush (Juncus gerardi) typically dominate
higher elevations.
3) The authors report that monitoring plant zonal boundaries
in two New England salt marshes revealed that low-marsh cordgrass
rapidly moved landward at the expense of higher-marsh species
between 1995 and 1998. Plant macrofossils from sediment cores
across modern plant community boundaries provided a 2500-year
record of marsh community composition and documented the
migration of cordgrass into the high marsh. Isotope dating
revealed that the initiation of cordgrass migration occurred in
the late 19th century and continued through the 20th century. The
timing of the initiation of cordgrass migration is coincident
with an acceleration in the rate of sea-level rise recorded by
the New York tide gauge.
4) The authors suggest these results indicate that increased
flooding associated with accelerating rates of sea-level rise has
stressed high-marsh communities and promoted landward migration
of cordgrass. If current rates of sea-level rise continue or
increase slightly over the next century, New England salt marshes
will be dominated by cordgrass. If climate warming causes sea-
level rise rates to increase significantly over the next century,
these cordgrass dominated marshes will likely drown, resulting in
extensive losses of coastal wetlands.
-----------
Proc. Nat. Acad. Sci. 2001 98:14218
-----------
ScienceWeek 22 Mar 2002 www.scienceweek.com
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
20. ON ENERGY SOURCES
M.S. Dresselhaus and I.L. Thomas (Massachusetts Institute of
Technology, US) discuss energy sources, the authors making the
following points:
1) Modern lifestyles demand a steady and reliable supply of
energy, and such energy lies at the heart of our mobility, our
prosperity, and our daily comfort. Energy security, however,
cannot be taken for granted.
2) Energy sources can be divided into 3 broad categories.
The first derives from chemical or photophysical energy that
relies on oxidizing some reduced substance, usually a
hydrocarbon, or absorbing sunlight to generate either heat or
electricity. The energy involved is that of a chemical bond or
fractions of an electron volt (eV). The second category of energy
source involves nuclear reactions that release energy either by
splitting heavy nuclei or by fusing light nuclei. The energy
involved in nuclear reactions is in the region of 10^(6) electron
volts (MeV) per nuclear reaction. The third category of energy
source is thermomechanical in the form of wind, water, or
geologic sources of steam or hot water. The energy involved is in
the milli-electron-volt (meV) region, e.g., energy from water
falling several tens of meters.
3) Each energy source has some undesirable characteristics.
Any process using fossil fuel produces carbon dioxide, and
perhaps also other contaminants, such as nitrogen oxides, sulfur
oxides, and ash. Nuclear plants produce radioactive fission
products. Hydroelectric plants require dams and large lakes.
Solar energy and wind energy require large areas and are limited
geographically. Geothermal sources are limited to very few
locations. Schemes using small temperature gradients in the Earth
or oceans have low thermal efficiencies, and thus require very
large heat-exchanger areas.
4) At present most of the world's energy supply comes from
fossil and nuclear sources. And although mankind is increasingly
having to face the issues of resource limitation and
environmental pollution, these sources will continue to be
important in providing energy worldwide for the next few
generations.
-----------
Nature 2001 414:332
-----------
ScienceWeek 22 Mar 2002 www.scienceweek.com
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
21. ON ENZYMATIC POLYMERIZATION
S. Kobayashi et al (Kyoto University, JP) discuss enzymatic
polymerization, the authors making the following points:
1) In this context, "enzymatic polymerization" is defined as
chemical polymer synthesis in-vitro (in test tubes) via non-
biosynthetic (non-metabolic) pathways catalyzed by an isolated
enzyme. Accordingly, polymer syntheses involving a living system,
e.g., fermentation and bacterial processes, are not included.
2) Many families of enzymes can be used for transformation
of not only their natural substrates but for transformation of a
wide range of unnatural compounds, yielding a variety of useful
materials. Employing enzymes in organic synthesis has several
advantages: a) catalysis under mild reaction conditions with
regard to temperature, pressure, and pH, which often leads to
remarkable energy efficiency; b) high enantio-, regio-, and
chemoselectivity as well as regulation of stereochemistry,
providing development of new reactions to functional compounds
for pharmaceuticals and agrichemicals; c) nontoxic natural
catalysis with "green" appeal of commercial benefit that
satisfies ecological requirements.
3) Concerning polymers, all naturally occurring polymers are
produced in-vivo by enzymatic catalysis. In-vitro synthesis of
polymers through enzymatic catalysis ("enzymatic polymerization")
has recently been extensively developed in various laboratories,
and enzyme catalysis has provided a new synthetic strategy for
useful polymers, most of which are otherwise extremely difficult
to produce by conventional chemical catalysis. In-vitro enzymatic
synthesis of polymers via non-biosynthetic pathways, therefore,
is now recognized as a new area of precision polymer synthesis.
Typical polymers now produced by enzymatic catalysis include
polyphenols, polyanilines, vinyl polymers, polysaccharides,
cyclic oligosaccharides, polyesters (all produced by
oxidoreductases and transferases); polysaccharides, polyesters,
polycarbonates, polyamine acids (all produced by hydrolases).
-----------
Chem Revs. 2001 101:3793
-----------
ScienceWeek 22 Mar 2002 www.scienceweek.com
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
22. SEMICONDUCTOR LASERS AND DELAYED OPTICAL FEEDBACK
T. Heil et al (Technical University Darmstadt, DE) discuss
delayed optical feedback, the authors making the following
points:
1) Delayed-feedback-dominated systems are encountered
extensively in the physical world and are of fundamental
importance. They are found in models of diffusion and
thermochemical reactions. In biology, they occur in blood-cell
production, neural control, and drug delivery, and have
applications in respiratory physiology. Physical understanding of
the dynamics of delay systems has increased during recent years
as a result of investigations involving semiconductor lasers
subject to delayed optical feedback, and basic nonlinear
dynamical phenomena have already been observed in this system. In
parallel, semiconductor lasers are of essential importance for
modern telecommunications, data transmission, and data storage
technologies, domains where the performance of semiconductor
laser systems is often degraded due to instabilities caused by
even small amounts of unavoidable optical feedback from distant
reflectors, for example, from the facet of an optical fiber or
compact disc. The consequence is the necessity for careful
isolation of the laser, thus increasing the complexity and cost
of such systems. Understanding of delayed-feedback-induced
instabilities and their fundamental dynamical phenomena is
therefore indispensable for a wide range of practical
applications.
2) The authors provide experimental and numerical evidence
for a new dynamical regime in the operation of semiconductor
lasers subject to delayed optical feedback occurring for short
delay times. The short cavity regime involved is dominated by a
striking dynamical phenomenon: regular pulse packages forming a
robust low-frequency state with underlying fast and regular
intensity pulsations. The authors demonstrate by numerical
analysis of the behavior of the differential equations of the
model describing this system that these regular pulse packages
correspond to phase-space trajectories moving on global orbits
comprising several destabilized fixed points within the
complicated phase space structure of this delay system.
-----------
Phys. Rev. Lett. 2001 87:243901
-----------
ScienceWeek 22 Mar 2002 www.scienceweek.com
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
23. ON CHARGE TRANSPORT IN DNA
M. Bixon and J. Jortner (Tel Aviv University, IL) discuss charge
transport in DNA, the authors making the following points:
1) Apart from the fundamental interest in the electronic
properties of DNA in the context of radiation damage and repair,
novel research areas concerning the dynamics, response, and
function of nanostructures and biosensors are emerging, and DNA-
based molecular electronic devices are expected to utilize the
unique features of recognition, assembly, and specific binding
properties of the nucleobases.
2) The DNA duplexes may serve as conducting building blocks
or as insulating (or conducting) templates for the assembly of
other electrically active nanoelements, e.g., semiconducting or
metal clusters. While at present nanoelectronic DNA-based systems
still constitute "theoreticians' dreams", the elucidation of the
mechanism and dynamics of charge transport/transfer in DNA is of
central importance.
3) The majority of the experimental information on charge
transport in DNA concerns positive charge (hole) migration, i.e.,
the propagation of a radical cation along the duplex. In view of
the hierarchy of oxidation potentials of single nucleobases in
solution, and of the ionization potentials of single nucleobases
and of nucleobases in duplexes, researchers have inferred that
"hole-hopping" occurs between guanine (G) nucleobases. Recent
computational results demonstrate that guanine nucleobases act as
"resting" lowest energy states for holes in DNA duplexes, while
GG and GGG fragments act as hole traps in DNA, in agreement with
experimental data.
-----------
J. Am. Chem. Soc. 2001 123:12556
-----------
ScienceWeek 22 Mar 2002 www.scienceweek.com
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
24. ON MIXING IN MICROCHANNELS
The "Reynolds number" is a dimensionless number significant
in the modeling of any system in which the effect of viscosity is
important in controlling flow velocities or flow patterns of a
fluid. The number equals the density of a fluid times its
velocity times a characteristic length for the system divided by
the fluid viscosity. In the Navier-Stokes equation describing the
flow of a Newtonian fluid, the Reynolds number appears as the
coefficient of a nonlinear term, and a large Reynolds number
makes a solution of the equation impossible. In many practical
systems, simple calculation of the Reynolds number provides an
estimate of whether the flow in the system will be laminar or
turbulent. A "Newtonian fluid" is a fluid in which the velocity
gradient is directly proportional to the shear stress.
In chemical engineering, the "Peclet number" is a
dimensionless group used to determine the chemical reaction
similitude for the scale-up from pilot-plant data to commercial-
sized units, the number incorporating heat capacity, density,
fluid velocity, and other relevant physical parameters.
... ... A.D. Strook et al (Harvard University, US) discuss mixing
in microchannels, the authors making the following points:
1) Microfluidic systems are now widely used in biology and
biotechnology. Applications include analysis of DNA and proteins,
sorting of cells, high-throughput screening, chemical reactions,
and transfers of small volumes (1 to 100 nanoliters) of
materials. Typical uses of microfluidic devices (e.g., chemical
analysis in the field) require that these systems be inexpensive
and simple to operate; microfluidic components that operate with
pressure flow and few moving parts are desirable. Microfluidic
designs should also be compatible with the planar, layer-by-layer
geometries that are imposed by current lithography-based
techniques of microfabrication.
2) Physically, flows of common liquids at practical
pressures in microfluidic channels (typical cross-sectional
dimension of 100 microns) are characterized by low values of the
Reynolds number, and general strategies for controlling flow in
microfluidic devices should not depend on inertial effects
because these only become important at a Reynolds number much
greater than 1.
3) It is difficult to mix solutions in microchannels. Under
typical operating conditions, flows in these channels are laminar
-- the spontaneous fluctuations of velocity that tend to
homogenize fluids in turbulent flows are absent, and molecular
diffusion across the channels is slow.
4) The authors report a passive method for mixing streams of
steady pressure-driven flows in microchannels at low Reynolds
number. Using this method, the length of the channel required for
mixing grows only logarithmically with the Peclet number, and
hydrodynamic dispersion along the channel is reduced relative to
that in a simple smooth channel. The method uses bas-relief
structures on the floor of the channel that are easily fabricated
with commonly used methods of planar lithography.
-----------
Science 2002 295:647
-----------
ScienceWeek 22 Mar 2002 www.scienceweek.com
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
25. IN FOCUS: ON JAMES CLERK MAXWELL (1831-1879)
"The theory that killed the static electron -- eventually known
as quantum mechanics -- evolved because physicists thought they
ought to know more about light. In fact they already knew a lot;
for instance they understood that light behaves as a wave. Waves
bend around obstacles in their path (a day on the beach observing
wave behavior may be in order), and waves interfere with each
other. If they are out of phase, they cancel one another to
create a calm; if they are in phase they combine to form larger
waves. Light also behaves this way. In-phase waves of light
projected through parallel pinholes create a pattern of
concentric rings of light and dark called an interference
pattern. Waves of *what* was not known until the work of James
Clerk Maxwell. Maxwell demonstrated that a moving electric charge
generates a magnetic field, and the magnetic field generates an
opposing electric field. The opposing electric field generates
and opposing magnetic field, and so on, with each field pushing
the other out of the way. When Maxwell calculated the speed at
which this occurs, he found it to be the known speed of light. He
must have said something like 'Aha'. Light, he had discovered, is
an oscillating electromagnetic wave. There is a story that
Maxwell was courting his wife at the time, and on the evening of
the day on which he came to this conclusion, they were walking in
a garden, gazing at the stars. He supposedly asked her how it
felt to be the only other person to know the true nature of
starlight. This may be a romanticized version of a true event
because we know Maxwell's wife later worked with him on his
experiments, so no doubt she discussed this important conclusion
with him. Later (after Maxwell's death at an early age) his
conclusion was confirmed experimentally by Heinrich Hertz [1857-
1894], who showed that a spark from two charged spheres sets up
an electromagnetic wave that can trigger a spark in similar
charged spheres a distance away (which eventually became the
basis for radio technology).
-----------
C. Cobb and H. Goldwhite: _Creations of Fire: Chemistry's Lively
History from Alchemy to the Atomic Age_
(Perseus Publishing, Cambridge MA 1995, p.313)
http://www.amazon.com/exec/obidos/ASIN/073820594X/scienceweek
-----------
ScienceWeek 22 Mar 2002 www.scienceweek.com
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
26. FROM THE SW ARCHIVE: CELL BIOLOGY: ON PROKARYOTES
One of the important concepts in current biology is the division
of living cells into prokaryotes and eukaryotes. In the 19th
century, it was already recognized that some types of cells
contain a nucleus and other distinctive structures, while other
cell types do not, but it was only in the 20th century,
especially after the advent of the electron microscope, that the
fundamental structural distinctions between prokaryotes and
eukaryotes became apparent. In general, eukaryotic cells are
defined as cells in which the bulk of genetic information is
contained in a nucleus surrounded by a double-membrane envelope,
while the genetic material of prokaryotic cells is not membrane-
enclosed. Prokaryotic cells include all forms of bacteria, while
eukaryotic cells comprise single-celled organisms other than
bacteria (e.g., algae, fungi, and protozoa), as well as the cells
of multicellular plants and animals. In addition to the absence
of a nucleus, also absent in prokaryotes (but generally present
in eukaryotes) are the following intracellular structures:
*endoplasmic reticulum, *Golgi complex, *lysosomes, *peroxisomes,
*nucleolus, *mitochondria, *chloroplasts, etc., all of which are
termed "organelles" of eukaryotic cells. There are other
structural distinctions, but these are the main differences
establishing the two types of living cells, prokaryotes and
eukaryotes.
... ... M. Hoppert and F. Mayer (2 installations, DE) present a
review of the internal organization of prokaryote cells, the
authors making the following points:
1) Throughout this century, cell biologists have refined
their understanding of the various compartments in eukaryotes.
Each such compartment is effectively a subcellular organ (an
"organelle") housing all the elements necessary to perform a
specific metabolic function. For example, mitochondria generate
chemical energy with which to power all the other activities of
the cell. Lysosomes and peroxisomes contain enzymes that degrade
molecules. Each organelle operates efficiently because it bundles
together all the biomolecules required to perform a particular
task. In contrast, prokaryotes lack membranous organelles and a
typical eukaryotic *cytoskeleton. Therefore, biomolecules in
prokaryotes are commonly believed to be scattered randomly
throughout the cytoplasm, with prokaryotic metabolism extremely
chaotic and inefficient. Actually, this common belief is false:
prokaryotic cells perform their biological functions with great
efficiency, and it appears that even without membrane-bound
compartments and a eukaryotic cytoskeleton, in prokaryotes the
molecules required for a particular metabolic activity are
grouped together into areas that are essentially "functional
compartments".
2) Prokaryotes such as bacteria are often described as "bags
of enzymes", but closer study reveals several levels of
subcellular organization. For example, in Escherichia coli, a
typical bacterium, there are several well-defined intracellular
compartments: a) the cell is surrounded by two membranes
enclosing a periplasmic compartment used for capturing and
sorting nutrients and wastes; b) at the center of the cell,
densely packed DNA strands are folded into a compact "nucleoid",
forming a loosely defined compartment devoted to the storage and
use of genetic information; c) the cytoplasm occupies the
remaining portions of the cell and is filled with *ribosomes and
many different enzymes. Multiprotein complexes are engaged in
many tasks: a) a *motor protein apparatus turns a long helical
flagellum to propel the cell through its environment; b)
*chaperonins and *proteasomes oversee the folding of new proteins
and the disposal of obsolete proteins, respectively; c) *DNA
polymerase copies the genetic information; d) various other
enzyme complexes perform sequential reactions with a number of
pathways linked together.
3) A striking example of functional compartmentalization is
the development by several forms of bacteria of enzymes that
attack and degrade cellulose, a tough and nearly indigestible
glucose polymer. In the bacterium Clostridium thermocellum, these
cellulose-degrading enzymes form a huge complex called the
"cellulosome" that is tethered to the surface of the cell, and in
the cellulosome a large "*scaffolding protein" organizes the
arrangement of the many digestive cellulase proteins.
4) In certain prokaryotes, entities known as "inclusion
bodies" have been recognized. These appear to be storage granules
enclosing large aggregates of water-insoluble materials such as
fats and starches. Materials inside the inclusion bodies are
degraded into smaller fragments that are released into the
cytoplasm when they are required to fuel a metabolic activity.
5) The authors suggest that when considering prokaryote
intracellular organization, it is important to include possible
microenvironments within the cytoplasm, one form of which may be
brought about by differential structures of water. The authors
propose that a boundary of *structured water approximately 2 to
10 nanometers thick can be found abutting a cell membrane and
other macromolecular cell structures. The authors suggest that
such intracellular layers of structured water in prokaryotes are
functional compartments that must be considered with other
functional compartments such as inclusion bodies, the nucleoid,
and other specialized macromolecular structures.
-----------
American Scientist 1999 87:518)
-----------
Notes:
... ... *endoplasmic reticulum: A complex system of flattened
sacs in eukaryotic cells, the site of many important syntheses,
apparently including the production of new surface membrane.
... ... *Golgi complex: The Golgi apparatus (Golgi complex) is a
collection of organelles (Golgi bodies) in eukaryotic cells that
essentially function as a collecting and packaging center for
substances that the cell manufactures for export.
... ... *lysosomes: A lysosome is a cytoplasmic membrane-bound
vesicle 5 to 8 nanometers in diameter and containing a variety of
glycoprotein hydrolytic enzymes used to digest foreign material
or defective organelles.
... ... *peroxisomes: A peroxisome is an organelle rich in
enzymes that act on or generate hydrogen peroxide.
... ... *nucleolus: A small dense body, rich in RNA and protein,
present in the nucleus of eukaryotes.
... ... *mitochondria: Organelles of the cell cytoplasm,
mitochondria are the principal energy source of the cell,
containing various enzymes involved in electron transport and
metabolic cycles.
... ... *chloroplasts: Cell organelles involved in
photosynthesis; they are found in all photosynthetic plant cells.
... ... *cytoskeleton: The quasi-rigid matrix that among other
things determines cell shape.
... ... *ribosomes: A ribosome (not to be confused with riboZYME)
is a small particle, a complex of various ribonucleic acid
component subunits and proteins that functions as the site of
protein synthesis.
... ... *motor protein: "Motor proteins" are mechanico-chemical
enzymes involved in locomotion or transport.
... ... *chaperonins: Chaperonins are a subclass of molecular
chaperones, proteins that assist in the correct folding of other
proteins without becoming actual components of the folding
proteins.
... ... *proteasomes: Large multi-subunit protease complexes that
selectively degrade intracellular proteins.
... ... *DNA polymerase: An enzyme that catalyzes the formation
of DNA polymers.
... ... *scaffolding protein: Any of a group of proteins that
have specific binding sites and are instrumental in determining
the structure and assembly of large 3-dimensional structures.
... ... *structured water: When ice melts to form liquid water,
the tetrahedral structure breaks down, but some hydrogen bonds
apparently continue to exist, and liquid water consists of groups
of associated water molecules mixed with some monomers and
dimers. That is one form of structured water. Another form of
structured water is the structure created by both the hydrogen
bonding and dipole properties of the water molecule when water
molecules are in an electric field produced by a macromolecule.
The current view is that water in association with charged
macromolecules (such as biomolecules) is in an ordered state. In
the context of this report, one would certainly expect various
intracellular macromolecular structures to have an organizing
effect on nearby water molecules, but it is not yet clear what is
happening in such regions and how it might effect biological
processes.
-----------
Related Background:
IN FOCUS: ON PROKARYOTIC AND EUKARYOTIC CELLS
"The oldest fossils known on Earth, found in South Africa,
Australia, and Siberia, indicate that the earliest forms of life
were individual (not colonial), single-celled, prokaryotic (pro
-- before; karyo -- kernel, a reference to the nucleus, or
central "kernel" of the cell) organisms. Prokaryotic cells are
small, have no nucleus or other internal partitions, and are the
type of cell found in bacteria. Today, along with prokaryotes,
however, there is a second very different kind of cell on Earth:
eukaryotes (eu -- true). Eukaryotic cells are larger and more
complex, and they have a nucleus and a variety of internal
chambers called 'organelles', each with specific functions. All
single-celled organisms [other than prokaryotes], as well as
multicellular life, are eukaryotic. The evolution of eukaryotes
from prokaryotes, arguably the single most significant event in
the history of life, probably occurred about 1.5 billion years
ago. An evolutionary step of this magnitude is hard to explain,
but one very plausible scenario, proposed in the late 1960s by L.
Margulis of the University of Massachusetts, suggests that
eukaryotic cells are in fact the products of prokaryotic cells
initially having been swallowed by other prokaryotes. This
theory, called the 'endosymbiotic theory' of the origin of
eukaryotes (endo -- inside; symbios -- living together), proposes
that the ingested prokaryotes continued to live with within their
hosts in a mutually beneficial arrangement, adopting specialized
functions as organelles. A large body of evidence supports this
theory. For example, the DNA and RNA of certain organelles is
like that of prokaryotic cells and different from that of the
nucleus; certain organelles have a separate cell membrane; and
organelles have separate reproductive mechanisms. Moreover,
chemical reactions within the tissue of eukaryotic cells are not
like those of certain organelles, whose own chemical reactions
more closely resemble those found in prokaryotes. Clearly,
evolution does not necessarily proceed in tiny mutation-based
steps occurring over millions of years!"
-----------
D.E. Fastovsky and D.B. Weishampel: _The Evolution and Extinction
of the Dinosaurs_.
(Cambridge University Press, New York 1996, p.67)
-----------
Related Background:
ON PROKARYOTES IN THE BIOSPHERE
Prokaryotes (bacteria) are unicellular life forms lacking a
membrane-bound nucleus, structured chromosomes, and complex
internal organization. They are invisible to the naked eye, but
they are an essential component of the Earth's biota. They
catalyze unique and indispensable transformations in the
biogeochemical cycles of the biosphere, produce important
components of the Earth's atmosphere, and represent a large
portion of life's genetic diversity. Although the abundance of
prokaryotes has been estimated indirectly, the actual number of
prokaryotes and the total amount of their cellular carbon on
Earth has never been directly assessed. ... ... Whitman et al (3
authors at University of Georgia, US) present an array of
calculations based on analysis of various habitats, and make the
following points: 1) The number of prokaryotes and the total
amount of their cellular carbon on Earth are estimated to be 4-6
x 10^(30) cells and 350-550 x 10^(15) grams of carbon,
respectively. The total amount of prokaryotic carbon is thus 60
to 100 percent of the estimated total carbon in plants, and
inclusion of prokaryotic carbon in global models will almost
double estimates of the amount of carbon stored in living
organisms. 2) In addition, the Earth's prokaryotes contain 85-130
x 10^(15) grams of nitrogen, and 9-14 x 10^(15) grams of
phosphorus, or about 10-fold more of these nutrients than do
plants, and represent the largest pool of these nutrients in
living organisms. 3) Most of the Earth's prokaryotes occur in the
open ocean, in soil, and in oceanic and terrestrial subsurfaces,
where the numbers of cells is of the order of 10^(29) to 10^(30).
4) The numbers of heterotrophic prokaryotes (bacteria that feed
on organic material) in the upper 200 meters of open ocean, the
ocean below 200 meters, and soil are consistent with average
turnover times of 6-25 days, 0.8 years, 2.5 years, respectively.
An uncertain estimate for the average turnover time of
prokaryotes in the subsurface is of the order of 1000 to 2000
years. 5) The cellular production rate for all prokaryotes on
Earth is estimated at 1.7 x 10^(30) cells per year and is highest
in the open ocean. The authors suggest that the large population
size and rapid growth of prokaryotes provides and enormous
capacity for genetic diversity, and that given the numerical
abundance and importance of prokaryotes in biogeochemical
transformations, the absence of detailed knowledge of prokaryotic
diversity is a major omission in our knowledge of life on Earth.
-----------
Proc. Nat. Acad. Sci. US 1998 95:6578
-----------
ScienceWeek 22 Mar 2002 www.scienceweek.com
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
In the text, the affiliation following the names of authors in
sources with more than one author is the affiliation of the lead
author.
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
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:
Professional Personal Subscriptions: 1 year $50, 2 years $80
Student Subscriptions: 1 year $25
Institutional Subscriptions: 1 year $200, 2 years $350
Further information concerning subscriptions is available at:
http://www.scienceweek.com/subinfo.htm
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
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) 1997-2002 SCIENCE-WEEK
All Rights Reserved
US Library of Congress ISSN 1529-1472
---------------------------------------------
ScienceWeek/Spectrum Press Inc.
3023 N. Clark Street #109
Chicago, 60657-5205 IL, USA.
---------------------------------------------
-----end file
|