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ScienceWeek
SCIENCE-WEEK - January 25, 2002 - Vol. 6 Number 4
An Email Research Digest Published Weekly Since 1997
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We are the strangest species. We question everything,
measure the stars, sift the sand through our fingers,
gauge the bowels of the Earth. It is our destiny and
it will not stop.
-- Unknown
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Section 1
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Contents of this Issue (Full reports in Section 2):
1. ABC Transporters
2. Innate versus Adaptive Immunity
3. Ancestry of Whales
4. Visualization of Lipid Rafts in Model Membranes
5. On the Physiology of Zinc
6. Regulated Destruction of Cell-Cycle Regulators
7. A New Test of Special Relativity Theory
8. On Stochastic Resonance
9. Suppression of Crystal Nucleation in Polydisperse Colloids
10. On the Amplification of Chirality
11. Water-Ice Chemistry of the Interstellar Medium
12. Composition of the Early Universe
13. PostDoctoral Fellowship Profile:
Laboratory of H.S. Bernstein, Univ. of California San Francisco
14. In Focus: On Continental Drift and Plate Tectonics
15. From PRAXIS: On the Etiology of Parkinson Disease
16. This Week in PRAXIS
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Section 2
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1. ABC TRANSPORTERS
C.F. Higgins and K.J. Linton (Imperial College, UK) discuss ABC
transporters. A biological cell must selectively translocate
molecules across its plasma membrane to maintain the chemical
composition of its cytoplasm distinct from that of the
surrounding milieu. The most intriguing and arguably the most
important membrane proteins for this purpose are the ABC (ATP-
binding cassette) transporters. These proteins, found in all
species, use the energy of ATP hydrolysis to translocate specific
substrates across cellular membranes. The chemical nature of the
substrates handled by ABC transporters is extremely diverse --
from inorganic ions to sugars and large polypeptides -- yet ABC
transporters are highly conserved in evolution. Mutations in the
genes encoding many of the 48 or so ABC transporters of human
cells are associated with diseases such as cystic fibrosis,
adrenoleukodystrophy, Tangier disease, and obstetric cholestasis.
Overexpression of certain ABC transporters is the most frequent
cause of resistance to cytotoxic agents such as antibiotics,
antifungals, herbicides, and anticancer drugs. As molecules, ABC
transporters comprise 4 "core" domains. Two transmembrane domains
form a pathway across the membrane through which solutes move,
and these domains consist of multiple membrane-spanning segments
(proposed to be alpha-helices) and contain the substrate binding
sites. The other two domains are highly conserved nucleotide-
binding domains located at the cytoplasmic face of the membrane
and these domains couple ATP hydrolysis to substrate
translocation. In general, ABC transporters are conventional
enzymes that undergo a conformation change in response to ATP
binding and hydrolysis.
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Science 2001 293:1782
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2. ON INNATE VERSUS ADAPTIVE IMMUNITY
N. Silverman and T. Maniatis (Harvard University, US) discuss
immunity. Innate immunity is the first line of defense against
infectious microorganisms. The innate immune system relies on
germ line-encoded pattern recognition receptors to recognize
pathogen-derived substances. Activation of the innate immune
system through these receptors leads to the expression of a vast
array of antimicrobial effector molecules that attack
microorganisms at many different levels. The innate immune system
appears early in evolution, and the basic mechanisms of pathogen
recognition and activation of the response are conserved
throughout much of the animal kingdom. Insects, for example, have
a very potent innate immune response that effectively combats a
broad spectrum of pathogens. The fruit fly Drosophila can
withstand and clear bacterial burdens that relative to the size
of the host would be lethal to mammals. In contrast to innate
immunity, the adaptive immune system generates antigen-specific
receptors, antibodies, and T-cell receptors by somatic cell DNA
rearrangement. These receptors, found only in higher eukaryotes,
recognize specific pathogen-encoded proteins. Mammals have a
complex immune response, which relies on communication between
the innate and adaptive arms of the immune system. The innate
immune response generates a "costimulatory signal", which is
required in combination with antigen-specific recognition to
activate T-cells and the adaptive immune system. Antigen-specific
recognition in the absence of co-stimulation can lead to absence
of response (anergy) rather than to activation. Thus, the
activation of an antigen-specific response is coupled to
infection through the innate immune system.
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Genes and Development 2001 15:2321
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SCIENCE-WEEK 25 Jan 2002 http://scienceweek.com
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Related Background:
MEDICAL BIOLOGY: ON THE IMMUNE SYSTEM
Our environment is filled with a variety of infectious agents,
including bacteria, viruses, parasites, and fungi, and the
essential line of defense against these pathogenic invaders is
the "immune system". This system, an evolutionary development in
vertebrates, involves a complex set of dynamic interactions
between various specialized cells, the interactions mediated by
chemistry. An important component is an evolved genomic apparatus
that essentially provides for an "immune memory", which in
general is a capability of the immune system to modify and
enhance its responses based on its previous experience with
particular pathogens. Nowhere is the idea of the human body as a
colony of cells more clear than in consideration of the
cooperative interactions of the various cells of the immune
system functioning to protect the entire organism.
... ... P.J. Delves and I.M. Roitt (University College London,
UK) present an extensive 2-part review of current knowledge
concerning the human immune system, the authors making the
following points:
1) In humans, there are two fundamentally different types of
responses to invading microbes: a) innate (natural) responses
that occur to the same extent however many times the infectious
agent is encountered; b) acquired (adaptive) responses that
improve after repeated exposure to a given infection.
2) The innate immune response involves a) various
specialized "phagocytes" (neutrophils, monocytes, macrophages),
cells that "eat" pathogens; b) various cells (basophils, mast
cells, eosinophils) that release *inflammatory mediator
substances; c) *natural "killer" cells. The molecular components
of innate responses include a variety of identified proteins
(e.g., *complement, *cytokines).
3) The acquired immune response involves the proliferation
of *antigen-specific *B and T cells, which occurs when the
surface receptors of these cells bind to antigen. Specialized
cells, called "antigen-presenting cells", display the antigen to
*lymphocytes and collaborate with them in the response to the
antigen. B cells secrete *immunoglobulins, the antigen-specific
*antibodies responsible for eliminating extracellular
microorganisms. T cells help B cells to make antibody and can
also eradicate intracellular pathogens by activating macrophages
and by killing virally infected host cells. In general, innate
and acquired responses usually work together to eliminate
pathogens.
4) The various cells of the immune system develop from
*pluripotent stem cells in the fetal liver and in bone marrow and
then circulate throughout the extracellular fluid. B cells reach
maturity within the bone marrow, but T cells must travel to the
thymus gland to complete their development.
5) Adaptive immune responses are generated in the *lymph
nodes, spleen, and *mucosa-associated lymphoid tissue, all of
which are called "secondary lymphoid tissues": a) In the spleen
and lymph nodes, the activation of lymphocytes by circulating
antigen occurs in distinctive B cell and T cell compartments of
lymphoid tissue. b) The mucosa-associated lymphoid tissues,
including the tonsils, adenoids, and *Peyer's patches, defend
mucosal surfaces. c) Diffuse collections of lymphoid cells are
present throughout the lung and *lamina propria of the intestinal
wall.
6) To establish an infection, a pathogen must first overcome
numerous surface barriers, such as enzymes and mucus, that are
either directly antimicrobial or that inhibit attachment of the
microbe. Because neither the *keratinized surface of the skin nor
the mucus-lined body cavities are ideal habitats for most
organisms, microbes must breach the *ectoderm. Any organism that
breaks through this first barrier encounters the two further
levels of defense, the innate and acquired immune responses.
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New Engl. J. Med. 2000 343:37,108
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Notes:
... ... *inflammatory mediator substances: 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.
... ... *natural "killer" cells: Cells of the innate immune
response that recognize and then kill abnormal cells such as
certain infected cells and tumor cells.
... ... *complement: A group of 9 interacting serum proteins,
mostly enzymes, which are activated during the immune response,
and which participate in bacterial lysis (destruction of bacteria
by disruption of cell membrane) and macrophage chemotaxis
(chemical attraction of macrophages, immune system amoeba-like
cells active in phagocytosis of bacteria and other particulates.)
... ... *cytokines: A cytokine is any substance that promotes
cell growth and cell division. Cytokines mediate many functions
of the immune system.
... ... *antigen: In general, an antigen is any entity that
provokes an immune response, and this includes, in certain
disease states, entities that are not "foreign" to the body.
... ... *B and T cells: (B and T lymphocytes) Lymphocytes (lymph
cells, lympho-leukocytes) are a type of leukocyte (white blood
cell) responsible for the immune response. In general, there are
two classes of lymphocytes: 1) the B-cells, when presented with a
foreign chemical entity (antigen), change into antibody producing
plasma cells; 2) the T-cells, which interact directly with
foreign invaders such as bacteria and viruses, and some types of
which assist B-cells in the B-cell response. The general
terminological differentiation between B-cells and T-cells is
based on where the cells mature: B-cells mature in (b)one marrow,
and T-cells mature in the (t)hymus gland.
... ... *lymphocytes: See above note.
... ... *immunoglobulins: (antibody): The immunoglobulins are a
large glycoprotein category that includes antibodies as a subset.
In general, an "antibody" is a protein molecule produced by the
immune system of vertebrate organisms, the molecule designed to
specifically interact with a particular antigen.
... ... *antibodies: See above note.
... ... *pluripotent stem cells: In general, the term "stem"
cells refers to undifferentiated cells that upon differentiation
can give rise to various specialized cell lines such as blood
cells, skin cells, nerve cells, etc. Adult bone marrow, for
example, contains stem cells that are the precursors of the
various specialized types of blood cells. "Pluripotent stem
cells" are stem cells that have the capacity to differentiate
into various cell types.
... ... *lymph nodes: The lymphatic system is a complex network
for the distribution of lymph fluid (which is similar to blood
plasma -- blood without red cells). Lymph is collected by
drainage from the tissues throughout the body, flows in the
lymphatic vessels through the lymph nodes, and is eventually
added to the venous blood circulation. Lymph consists of a clear
liquid portion, varying numbers of white blood cells (chiefly
lymphocytes), and a few red blood cells. The lymph nodes are
small bodies located throughout the lymph system and varying in
diameter from 0.1 to 2.5 centimeters.
... ... *mucosa: In general, a multilayer tissue lining various
tubular structures in the body.
... ... *Peyer's patches: Aggregated lymphoid nodules of the
small intestine.
... ... *lamina propria: The layer of connective tissue
underlying the *epithelial layer of a mucosa.
... ... *epithelial layer: In animals and humans, epithelial
cells compose the cell layers that form the interface between a
tissue and the external environment, for example, the cells of
the skin, the lining of the intestinal tract, and the lung airway
passages.
... ... *keratinized: Keratin is a protein which helps waterproof
and protect the skin and underlying tissues.
... ... *ectoderm: In the embryos of higher animals, there
occurs the transformation of a single-layer "blastula" into a
3-layered "gastrula" consisting of ectoderm (outermost layer),
mesoderm (middle layer), and endoderm (innermost layer)
surrounding a cavity with one opening. The 3 layers are called
the "germ layer", and these layers, via further cell
differentiation and proliferation, determine the development of
all the major body systems and organs.
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SCIENCE-WEEK 2000 21 Jul
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Related Background:
ON MODELS OF IMMUNE MEMORY
Higher vertebrates, including humans, have through evolution
developed an immune system that can selectively destroy or
inactivate foreign molecules and foreign cells (*antigens)
without harming the molecules or normal cells of the host. The
vertebrate immune system apparently retains a "memory" of each
antigen attack, allowing the immune system to respond more
efficiently the next time it encounters the same invader. One
group of immune system cells involved in this immune system
memory is a small fraction of the proliferating *B-lymphocyte
cell population, the fraction effectively set aside as a reserve
population of cells to be directed against a specific stimulating
antigen. Such cells, called "memory B cells", are
indistinguishable in appearance from other unstimulated
lymphocytes and like them do not secrete antibody. But if the
organism is exposed to the same antigen a second time, the
reserve population of antigen-specific memory cells quickly
proliferates and differentiates into antibody-secreting plasma
cells, thereby allowing what is called the "secondary response"
to a given antigen to occur more rapidly and produce more
antibody than the initial or "primary response". The
effectiveness of the secondary response is the apparent reason
why humans, for example, rarely contract such diseases as chicken
pox or mumps more than once. One of the central problems in
immunology is to provide a molecular explanation for immune
system memory (also called "immune memory). There has been much
debate concerning the relative contributions to immune memory of
processes such as the persistence of antigens, *cross-reactive
stimulation, *homeostasis, competition between different lineages
of lymphocytes, and the rate of cell turnover
... ... R. Antia et al (3 authors at 2 installations, US) present
several mathematical models designed to investigate the
contributions of the various processes to the longevity of immune
memory. The authors define immune memory as the maintenance of an
elevated population of antigen-specific cells, and they define
the longevity of immune memory as the rate of decline of the
population of antigen-specific memory cells. The models presented
by the authors incorporate a repertoire of immune cells, each
lineage with distinct antigenic specificities, the basic
equations describing the dynamics of individual lineages and the
total population of cells. The authors suggest their results
indicate that if homeostatic control regulates the total
population of memory cells, then immune memory will be long-lived
(half-life > 1 year). The authors also suggest that the longevity
of immune memory in this situation will be insensitive to the
relative rates of cross-reactive stimulation, the rate of
turnover of immune cells, and the functional form of the
mathematical term for the maintenance of homeostasis. Further,
the authors suggest their models predict that when the frequency
of antigenic stimulation from other infectious agents is very
high, the duration of immune memory is likely to be relatively
low: i.e., sufficiently frequent exposure to new pathogens will
result in a relatively high rate of decline of immune memory with
respect to a given pathogen.
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Proc. Natl. Acad. Sci. 1998 95:14926
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Notes:
... ... *antigens: See main report.
... ... *B-lymphocyte cell: See main report.
... ... *cross-reactive stimulation: In general, in this context,
a "cross-reaction" is an immunological phenomenon in which an
antigen reacts with an antibody that has been raised (produced)
against a different antigen. The term "cross-reactive
stimulation" refers to the production of cross-reacting antibody
(or immune cell), i.e., an antibody (or immune cell) able to
react with an antigen that did not specifically stimulate its
original production.
... ... *homeostasis: The term "homeostasis" refers to a
physiological equilibrium necessary in general for the viability
of an organism, and in particular for the operation of many
cellular functions. Homeostatic mechanisms in biological systems
usually involve an element of negative feedback signaling. In
vertebrates, for example, when blood temperature is too high,
temperature receptors provoke a sequence of events involving many
pathways that ultimately results in a lowering of body
temperature. Similar homeostatic mechanisms operate at cellular
levels.
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SCIENCE-WEEK 1999 12 Feb
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3. ON THE ANCESTRY OF WHALES
Kenneth D. Rose (Johns Hopkins University, US) discusses the
ancestry of whales. Whales are mammals that apparently moved to
the sea approximately 50 million years ago, and exactly how
whales are related to other mammals has long been one of the most
vexing questions facing mammologists and paleontologists. In the
last decade, mounting evidence that whales are highly specialized
ungulates (hoofed mammals) has been bolstered by the discovery of
an impressive array of previously unknown fossil whales in
Pakistan, India, and Egypt, fossils that largely fill the
morphological gulf between land mammals and ocean-dwelling
cetaceans (whales, dolphins, and porpoises). The move to the
ocean required many adaptations to living in water, but the
earliest whales still closely resembled land animals. One of the
most spectacular transitional forms is the "walking whale"
Ambulocetus from the middle Eocene (approximately 47 to 48
million years ago. This species had relatively well-developed
limbs, paraxonic feet (where the plane of symmetry passes between
the third and fourth digits), and hoof-like terminal toe bones.
But fossils have failed to provide conclusive indications of the
closest relatives of whales, and instead have sparked new
controversy. Most recent morphological analyses suggest that the
mesonychians, an extinct group of terrestrial carnivorous
ungulates, form the sister group of cetaceans. Molecular
systematists, however, maintain that cetaceans belong to the
artiodactyls (even-toed ungulates such as sheep, cows, pigs,
camels, deer, and hippos) and are in fact the sister group of
hippopotami. Now Gingerich et al (2001) report important new
fossil evidence -- skeletons of two very primitive ancient whales
with well-developed limbs from the middle Eocene of Pakistan --
that moves the dispute closer to resolution. The new fossils
provide compelling morphological evidence that whales are not
merely related to but descended from artiodactyls rather than
from mesonychians, thus bringing the morphological evidence into
agreement with molecular data, at least at the level of taxonomic
orders.
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Science 2001 293:2216,2239
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4. VISUALIZATION OF LIPID RAFTS IN MODEL MEMBRANES
Deborah A. Brown (State University of New York Stony Brook, US)
discusses lipid rafts. The question of whether membrane lipids
mix uniformly or are arranged in discrete microdomains has vexed
membrane biochemists since the structure of the membrane bilayer
was first elucidated. The last few years have seen the emergence
of interest in one type of microdomain: lipid rafts, or
sphingolipid-rich domains in the liquid-ordered phase. The raft
hypothesis states that separation of discrete liquid-ordered and
liquid-disordered phase domains occurs in membranes containing
sufficient amounts of sphingolipid and sterol. Although
significant evidence for the existence of rafts has been
presented, compelling proof has remained elusive. The liquid-
ordered phase domains are proposed to have properties similar to
domains described in binary mixtures of a single order-preferring
phospholipid and cholesterol. They are fluid, and lipids in these
domains are believed to have a relatively high diffusion rate.
The acyl chains are tightly packed and highly ordered. Lipids and
proteins that prefer such an ordered environment are proposed to
partition favorably into the liquid-ordered phase domains and
thus to be enriched in rafts. Now Dietrich et al (2001) have
pioneered a new approach that allows direct microscopic
visualization in model membranes of domains with properties
expected of rafts, and the results support the tenets of the raft
hypothesis to a remarkable degree.
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Proc. Natl. Acad. Sci. 2001 98:10517,10642
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5. ON THE PHYSIOLOGY OF ZINC
M. Hershfinkel et al (Ben Gurion University of the Negev, IL)
discuss the physiology of zinc. Zinc is an essential
micronutrient involved in structural and regulatory cellular
functions. Zinc interacts with zinc-finger domains and acts as a
cofactor of numerous enzymes. Zinc ions also specifically bind to
many membrane receptors, transporters, and channels, thereby
modulating the activity of these entities. It is not surprising,
therefore, that zinc deficiency affects multiple organs,
including the digestive, immune, and neuronal systems. A severe
lack of zinc is linked to the attenuation of growth and sexual
development, and conversely, an excess of extracellular zinc is
considered toxic. Indeed, brain ischemia is accompanied by a
massive release of synaptic zinc permeating into neurons and
leading to neuronal cell death. Furthermore, striking changes in
plasma-zinc concentration occur during diverse pathophysiological
syndromes, including myocardial infarction, hepatic renal
failure, and neoplastic processes. Despite the large fluctuations
in extracellular zinc concentration and their consequent clinical
importance, little is known about cellular signaling mechanisms
that sense changes in extracellular-zinc concentration. The
authors describe a previously uncharacterized G-protein-coupled
receptor that specifically senses changes in extracellular zinc
concentration and subsequently triggers a release of
intracellular calcium, thereby modulating ion transport in
colonocytes. The authors suggest these findings provide evidence
for a specific zinc-sensing mechanism involving cellular
signaling and control of key cellular processes.
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Proc. Natl. Acad. Sci. 2001 98:11749
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Related Background:
ON ZINC IN BIOLOGICAL CELLS
Maureen Rouhi (CEN) discusses zinc in biological cells. A
bacterial cell contains up to 400,000 atoms of zinc, but new
research indicates that apparently none of these atoms are free
in the cell cytoplasm (cytosol). This result contradicts the
long-held assumption that pools of free zinc, and of other
transition metals such as copper, exist in biological cells.
According to this conventional view, metal-requiring proteins
newly synthesized by ribosomes would select ligands from the
pools of free metal. In contrast, the current growing view is
that zinc and other transition metals are always bound tightly by
biopolymers, and that the transport of metals within cells must
be kinetically controlled by metalloregulatory proteins and
perhaps by other entities such as "metal chaperones", which are
proteins that can mobilize bound metal and conduct it to sites
where it is required. There is already evidence that copper
chaperones help deliver copper to copper-requiring proteins, a
process apparently necessary to protect the cell from the
toxicity of copper. Zinc, however, is far less toxic and far more
abundant in cells than copper, and chaperoning based on toxicity
seems unnecessary. Instead, metal chaperones may be involved in
selection of sites among the many potential metal-binding sites.
There is evidence, for example, that zinc does not always end up
at the tightest binding sites or the first binding site
encountered, which suggests a special binding-site selection
process.
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Chem. & Eng. News 2001 17 Sep
Science 2001 292:2488
J. Am. Chem. Soc. 2001 123:8614
Biochemistry 2001 40:10417
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PRAXIS 29 Oct 2001 http://scienceweek.com/praxis
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Related Background:
BIOCHEMISTRY OF ZINC
S.C. Burdette et al (Massachusetts Institute of Technology, US)
discuss zinc ions in biological systems. Zinc is a vital
component in many cellular processes. Although traditionally the
study of the biochemistry of ionic zinc, Zn(sup2+), has focused
on its structural and catalytic functions in proteins, the
neurobiology of ionic zinc has been a subject of increasing
attention. Whereas most ionic zinc in biological systems is
tightly bound in proteins, a pool of free ionic zinc in cells has
been demonstrated, including sub-nanomolar concentrations in
undifferentiated mammalian cells, and higher concentrations
approaching 300 micromolar in the mossy fiber terminals of the
hippocampus. The zinc ion has the ability to modulate a variety
of ion channels, may play a role in neuronal death during
seizures, is pertinent to neurodegenerative disorders, and may be
vital to neurotransmission. The levels of ionic zinc in the brain
and other parts of the body are regulated by at least three
homologous ionic zinc-transport proteins and by metallothioneins
that are expressed mainly in the brain. Zinc transport proteins
and metallothioneins are probably responsible for distributing
the required amounts of ionic zinc to proteins and enzymes,
minimizing the amounts of free and potentially toxic levels of
ionic zinc present in cells. But in addition to protein
regulators, ionic zinc can be released from synaptic vesicles and
can enter cells via voltage-dependent calcium-ion channels,
indicating that free ionic zinc is available for neurological
functions. Limited methods for detecting ionic zinc in these
systems have hampered research. The authors report the synthesis
of two new fluorescent sensors for ionic zinc that utilize
fluorescein as a reporting group.
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J. Am. Chem. Soc. 2001 123:7831
ScienceWeek 2001 28 Sep
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PRAXIS 29 Oct 2001 http://scienceweek.com/praxis
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SCIENCE-WEEK 25 Jan 2002 http://scienceweek.com
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6. ON THE REGULATED DESTRUCTION OF CELL-CYCLE REGULATORS
M. Schwab and M. Tyers (Mount Sinai Hospital Toronto, CA) discuss
cell-cycle regulators and make the following points:
1) The "cell cycle" is the process by which cells grow,
replicate their genome, segregate the two copies of the genome,
and divide. The progression of these events is controlled by
enzymes known as "cyclin-dependent kinases" (CDKs), whose
activity in turn depends on their association with proteins
called "cyclins". For example, Cdk2 works with cyclin-E to
catalyze two key processes -- the start of DNA replication and
duplication of the centrosome, the precursor to the chromosome-
separating apparatus.
2) The onset and demise of CDK activity is controlled mainly
by the scheduled degradation of proteins that inhibit CDKs and
the degradation of cyclins. The timely appearance and
disappearance of cyclin-E is crucial: excessive activity of the
cyclin-E/Cdk2 complex drives cells to copy their DNA prematurely,
resulting in genome instability; moreover, cyclin-E levels are
often higher than normal in human tumors.
3) The programmed degradation of many proteins that regulate
the cell cycle is carried out by the ubiquitin-proteasome system.
A cascade of enzymes -- generically termed E1, E2, and E3 --
catalyzes the addition of polymers of the small protein ubiquitin
to the protein substrates, and this polyubiquitin tag acts as an
address label, directing substrates to a specific proteasome (26s
proteasome), where the tagged proteins are destroyed. Specificity
in the ubiquitin system is controlled largely by E3 enzymes, also
known as "ubiquitin ligases".
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Nature 2001 413:268
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7. A NEW TEST OF SPECIAL RELATIVITY THEORY
C. Braxmaier et al (University of Konstanz, DE) discuss a new
test of special relativity theory, the authors making the
following points:
1) Special relativity is one of the fundamental theories of
nature, and the prominent role of the theory as a basis of our
physical view of nature has motivated experimenters to test its
foundations and predictions with ever increasing accuracy. Added
motivation for tests is provided by the theoretical efforts to
unify the forces of nature. For example, approaches towards a
quantum theory of gravity have been put forward that lead to
modified Maxwell equations that are not necessarily Lorentz
covariant.
2) The relationships between gravity and the other forces of
nature can also be probed by measuring the gravitational
frequency shift ("redshift") of clocks based on these forces. The
principle of local position invariance implies that the
gravitational redshift is universal, i.e., independent of the
type of clock. Local position invariance, special relativity, and
the weak equivalence principle are the ingredients of the
Einstein equivalence principle. No simple way to quantize gravity
has been found: schemes aimed at quantization are found to lead
to violations of the Einstein equivalence principle at some level
of accuracy. Thus, it is important to improve the tests of local
position invariance.
3) Thanks to worldwide developments in frequency metrology
and ultrastable oscillators, especially in the optical domain,
there is now opportunity to improve our knowledge of special
relativity and local position invariance by several orders of
magnitude. The authors report on a first step in this direction,
the step based on a laboratory experiment. The experiment
involves a 190-day comparison of the optical frequencies defined
by an optical cavity and a molecular electronic transition, the
comparison analyzed for the velocity independence of the speed of
light (the so-called Kennedy-Thorndike test) and the universality
of the gravitational redshift. The modulations of the laboratory
velocity and the gravitational potential were provided by Earth's
orbital motion around the Sun. The authors suggest their
experiment provides new limits on violations of the Einstein
equivalence principle, and that their result improves the overall
accuracy of the verification of special relativity theory by a
factor of 3.
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Phys. Rev. Lett. 2002 88:010401
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8. ON STOCHASTIC RESONANCE
A.A. Zaikin et al (Potsdam University, DE) discuss stochastic
resonance, the authors making the following points:
1) It has been established that dynamical noise, which
usually has a disordering impact, can be used to induce order in
nonlinear nonequilibrium systems under certain conditions.
Examples of this counterintuitive influence of random
fluctuations are noise-induced transitions, stochastic transport
in ratchets (also in a synthesis with a transition), or noise-
induced pattern formation. However, one of the most significant
examples is "stochastic resonance", which has been experimentally
observed in several physical and biological systems.
2) In the classical situation, stochastic resonance consists
of an optimization by noise of the response of a bistable system
to a weak periodic signal. Besides this standard scenario,
stochastic resonance has also been found in monostable,
excitable, nondynamical systems, in systems without a threshold,
in systems without an external force (so-called "coherence
resonance"), and in systems with transient noise-induced
structure.
3) In addition, it has recently been demonstrated that the
energy of fluctuations can be used even more efficiently in
spatially extended systems by using noise twofold: to synchronize
output hops across a potential barrier with an external signal,
and also to optimally construct the barrier itself. This
phenomenon is known as "doubly stochastic resonance" and occurs
in systems of coupled overdamped oscillators. It is a synthesis
of two basic phenomena: stochastic resonance and noise-induced
phase transitions. Another important and nontrivial phenomenon
related to stochastic resonance in spatially distributed systems
is the phenomenon of "noise enhanced propagation", in which the
propagation of a harmonic forcing through an unforced bistable or
excitable medium is increased for an optimal intensity of the
additive noise.
-----------
Phys. Rev. Lett. 2002 88:010601
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SCIENCE-WEEK 25 Jan 2002 http://scienceweek.com
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9. SUPPRESSION OF CRYSTAL NUCLEATION IN POLYDISPERSE COLLOIDS
S. Auer and D. Frenkel (FOM Institute for Atomic and Molecular
Physics Amsterdam, NL) discuss crystal nucleation in colloids,
the authors making the following points:
1) The formation of small crystallites is governed by two
competing factors: a) the free energy gained upon transferring
constituent atoms, molecules, or colloidal particles from the
metastable liquid to the more stable solid, and b) the free
energy needed to create the surface area of the crystallite.
2) Because the ratio of surface area to bulk is large for
small particles, small crystallites dissolve spontaneously under
conditions where larger crystallites are stable, and macroscopic
crystal growth occurs only if spontaneously formed crystallites
exceed a critical minimum size.
3) On theoretical grounds, the probability of forming such
critical crystal nuclei is expected to increase rapidly with
supersaturation. However, experiments demonstrate that the rate
of crystal nucleation in many systems goes through a maximum as
the supersaturation is increased.
4) It is commonly assumed that the nucleation rate peaks
because, even though the probability of forming critical nuclei
increases with increasing concentration, the rate of growth of
such nuclei decreases.
5) The authors report simulations of crystal nucleation in
suspensions of colloidal spheres with varying size distributions
that demonstrate that the probability that critical nuclei will
form itself goes through a maximum as the supersaturation is
increased. The authors report they find that this effect, which
is strongest for systems with the broadest particle size
distributions, results from an increase with supersaturation of
the solid-liquid interfacial free energy. The magnitude of this
effect suggests that vitrification at high supersaturation should
yield colloidal glasses that are truly amorphous rather than
nano-crystalline.
-----------
Nature 2001 413:711
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SCIENCE-WEEK 25 Jan 2002 http://scienceweek.com
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10. ON THE AMPLIFICATION OF CHIRALITY
L.J. Prins et al (University of Twente, NL) discuss amplification
of chirality, the authors making the following points:
1) Amplification of chirality occurs in systems where a
small initial chiral bias induces a high diastereomeric excess or
enantiomeric excess. The main reason for the interest in this
phenomenon is its relevance to enantioselective synthesis.
2) Asymmetric autocatalytic reactions and nonlinear effects
have been extensively studied to develop systems that display a
strong amplification of chirality, and from a broader
perspective, the phenomenon is also regarded as essential for the
explanation of homochirality in nature.
3) In 1989, Green et al reported the amplification of
chirality in the synthesis of polyisocyanates having a stiff
helical backbone based on the cooperative action of individual
small forces. The macromolecular helicity of these polymers can
be quantitatively controlled via the incorporation of asymmetric
centers in the side chains. Green et al (1989) found that the
chiroptical properties of the polymer did not change when the
ratio of chiral to achiral monomers was substantially lowered.
Even polymers containing only 0.5 percent of chiral monomers
still expressed a strong chiroptical activity.
4) The reason for this strong amplification is that the
achiral components "follow" the helicity induced by the chiral
components, and this is commonly referred to as the "Sergeants
and Soldiers Principle". It is a general phenomenon applicable to
other polymers with stiff helical backbones.
5) The authors report simulations that demonstrate that it
is theoretically possible that the diastereomeric excess in a
dynamic system is more than 99 percent with less than 1 percent
chiral component present.
-----------
J. Am. Chem. Soc. 2001 123:10153
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SCIENCE-WEEK 25 Jan 2002 http://scienceweek.com
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11. WATER-ICE CHEMISTRY OF THE INTERSTELLAR MEDIUM
F. Borget et al (University of Provence Marseille, FR) discuss
the chemistry of the interstellar medium, the authors making the
following points:
1) Up to 120 different molecules have been identified in the
interstellar medium, and to understand their formation and
evolution, numerous theoretical models, which include detailed
physical and chemical pathways, have been developed. However, for
these models, experimental data relating to grain surface
processes and chemistry in ices have been conspicuously absent.
The gas-grain interaction, involving heterogeneous reactions on
grain surfaces or in the icy mantles, is nevertheless assumed to
play an important role in the formation of molecules in the
interstellar medium.
2) Effectively, there are vast quantities of water ice in
the low-temperature region of the Solar System which have been
detected by infrared spectroscopy. Present on the satellites of
the outer planets and on comets, water ice is also believed to be
an important constituent of interstellar dust. Concerning the
pressure and temperature conditions existing in the interstellar
medium, it is reasonably expected that the ice is amorphous. For
these reasons, particular interest has been focused on small
molecules interacting with amorphous ice surfaces.
3) The physical and structural properties of amorphous solid
water have been the subject of numerous reports and reviews, and
from theoretical and experimental studies of ice clusters and
microporous amorphous ice, several aspects of the surface of ice
have been revealed. Detailed investigations coupled with computer
modeling have identified three characteristic water-ice surface
molecules: a) those with a dangling OH bond; b) those with a
dangling bond not occupied by H, called "dangling O"; and c) 4-
coordinated molecules, called "s-4", that are distorted from the
usual tetrahedral symmetry. In particular, it has been
established through spectroscopic studies that dangling OH groups
are abundant at the surface of both crystalline and amorphous
ice.
-----------
J. Am. Chem. Soc. 2001 123:10668
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SCIENCE-WEEK 25 Jan 2002 http://scienceweek.com
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Related Background:
ASTROBIOLOGY: SELF-ASSEMBLY OF AMPHIPHILIC MOLECULES IN A
MODEL OF INTERSTELLAR/PRECOMETARY ICES
In general, the term "interstellar medium" refers to the
matter contained in the region between the stars of our Galaxy,
this matter constituting approximately 10 percent of the Galactic
mass, and consisting of gas and interstellar dust. The
interstellar medium is not uniformly distributed through space,
but contains regions of high-density and low-density clouds. It
is the interstellar medium that provides the material from which
new stars are born.
In this context, the term "molecular cloud" refers to a cool
and dense region of interstellar matter within which atoms tend
to be combined into molecules. Such clouds are composed
principally of molecular hydrogen, with between 300 to 2000
molecules per cubic centimeter. Such clouds also contain an
admixture of "cosmic dust" comprising approximately 1 percent of
the mass, with gas temperatures between 10 and 20 degrees kelvin.
In astrophysics, the term "dust" refers to various entities:
a) interplanetary and cometary dust are found in the Solar
System; b) circumstellar dust is found around stars; c)
interstellar dust is found between stars. Individual dust
particles are usually called "dust grains" and range in size from
approximately 10 nanometers up to the micron range (with an
average size about the size of particles in cigarette smoke).
Interstellar dust extinguishes and reddens starlight, can be
detected by its absorption and emission of infrared radiation,
and can be detected by its polarizing effect on starlight. The
exact composition of interstellar dust is uncertain, but infrared
absorption measurements indicate that a significant fraction of
the material is organic. In general, interstellar dust is
believed to be carbon, iron, and silicates mixed with or coated
with frozen water.
"Planetesimals" are bodies with dimensions of 10^(-3) to
10^(3) meters that are believed to form planets by a process of
accretion. The term "accretion" refers to an aggregation, an
increase in the mass of a body by the addition of smaller bodies
that collide and adhere to it, provided the relative velocities
are low enough for coalescence. As the mass of the agglomerate
increases, so does the rate of accretion, and this accretion
process is believed to generally occur in the form of a disk. A
stellar accretion disk is a swarm of dust grains that evolve into
planetesimals and then planets.
The permanent solid portion of a comet (its "nucleus") is
believed to be a kilometer-sized solid mixture of dust and ice
("dirty snowball"), a model first suggest by Fred L. Whipple in
1951.
In general, "amphiphiles" are molecules with parts (groups)
having diverse affinities for different solvents. For example,
polar groups have an affinity for water, while hydrocarbon groups
have an affinity for oils. Most detergents are amphiphiles,
molecules with a polar head and a long hydrocarbon tail. In this
context, however, possible solvent interactions are only one
aspect of amphiphilic character. The important consideration is
that amphiphiles tend to self-organize: groups of amphiphilic
molecules will form stable domains of polar interactions and
nonpolar interactions. For example, amphiphiles may form
"micelles", spherical or cylindrical arrangements with an
interior forming one interaction domain while the surface forms
another interaction domain. Larger aggregates may form vesicles
with diameters in the micron range. Since biological membranes
consist largely of amphiphile lipids, many researchers believe
prebiotic chemical systems may have involved amphiphile vesicles.
... ... J.P. Dworkin et al (4 authors at 3 installations, US)
present a report of self-assembling amphiphilic molecules in a
laboratory model of interstellar dust and cometary ice, the
authors making the following points:
1) The authors point out that interstellar gas and dust are
believed to constitute the primary material from which the Solar
System formed. Near the end of the hot early phase of star and
planet formation, less refractory volatile materials were
transported into the inner Solar System as comets and
interplanetary dust particles. Once the inner planets had
sufficiently cooled, late accretionary infall seeded them with
complex organic compounds, and delivery of such extraterrestrial
compounds may have contributed to the organic inventory necessary
for the origin of life.
2) Interstellar ices, the building blocks of comets, contain
a large fraction of the biogenic elements available in molecular
clouds: infrared observations of molecular clouds, coupled with
laboratory studies, have demonstrated that water, methyl alcohol,
carbon monoxide, carbon dioxide, and ammonia are major components
of ices in such clouds. Energetic in situ processing of
interstellar ices into complex species can be driven by cosmic
ray-induced ultraviolet radiation in dense clouds, by the
significantly enhanced ultraviolet radiation field in star-
forming regions, and by high-energy particle bombardment and
ultraviolet radiation from the earliest stage ("T-Tauri phase")
of stellar birth. Laboratory studies have also demonstrated that
such energetic processing produces many new organic compounds in
these ices, including chemical species far more complex than the
starting materials. Given that this processing occurs wherever
new stars are being created, and that there is isotopic evidence
from meteorites and cosmic dust that these chemical species can
survive incorporation into newly-forming stellar systems and
subsequent delivery to planetary surfaces, this photochemical
processing may have played a significant role in prebiotic
chemistry.
3) The authors report the laboratory simulation of an
interstellar ice mixture that upon photolysis produces
amphiphilic vesicle-forming compounds similar to those found in
primitive meteorites such as the *Murchison carbonaceous
chondrite. Starting from a simple but astrophysically relevant
ice mixture (water, methanol, ammonia, and carbon monoxide), a
complex mixture of compounds, including fluorescent molecules and
molecules with observed amphiphile behavior, is generated on low-
temperature photolysis. The authors suggest that the ready
formation of these insoluble compounds from photolyzed ices
comprised of simple molecules indicates not only that this
process might be the source of their origin in meteorites, but
that the delivery of such compounds by comets, meteorites, and
interplanetary dust particles during the heavy bombardment period
of early Earth may have played an influential role in the origin
of terrestrial life. The authors also suggest that because their
experimental conditions for ice photolysis were designed to
simulate the environments of dense interstellar molecular clouds
(the birth sites of new stars and planetary systems), the
delivery of such compounds to the surfaces of newly-formed
planets may be a universal process.
4) Concerning the identities of the chemical species
produced by ultraviolet photolysis, the authors state:
"Unfortunately, there was insufficient material for further
analysis of most of these fractions. It is clear, however, that
each fraction contains numerous compounds, with possibly hundreds
of different molecules contained in the residue."
-----------
Proc. Natl. Acad. Sci. 2001 98:815
-----------
Notes:
... ... *Murchison carbonaceous chondrite: "Stony" meteorites
(aerolites) are meteorites formed solely of rock-forming
silicates, and chondrites are a type of stony meteorite
consisting of an agglomeration of millimeter-sized globules
(chondrules) that are thought to be unchanged since the original
condensation out of the nebula from which the Sun and
Solar System formed. A "carbonaceous chondrite" is a chondritic
meteorite that contains a relatively large amount of carbon, with
a resultant dark appearance. The "Murchison meteorite" is a
carbonaceous chondrite that fell in 1969 near Murchison,
Australia, the meteorite containing a variety of biologically
relevant molecules.
-----------
SCIENCE-WEEK 2001 30 Mar
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SCIENCE-WEEK 25 Jan 2002 http://scienceweek.com
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12. COMPOSITION OF THE EARLY UNIVERSE
Brian D. Fields (University of Illinois Urbana, US) discusses the
early Universe, the author making the following points:
1) We observe galaxies receding from us today and infer that
the Universe is expanding. In the past, therefore, matter in the
Universe was more concentrated. Extrapolating to very early
times, we conclude that the Universe was once very dense and very
hot. Big Bang nucleosynthesis and the cosmic microwave background
radiation follow from applying well-tested principles of atomic
and nuclear physics to this hot, dense, and rapidly expanding
early Universe.
2) Big Bang nucleosynthesis marks a milestone in the cosmic
history of ordinary matter or "baryons" (baryons are broadly
understood to be anything made of protons and neutrons, and thus
the term includes the entire periodic table). Big Bang
nucleosynthesis occurred between 1 second and approximately 3
minutes after the Big Bang, when matter was so hot (approximately
10^(9) kelvins) that not only were atoms ionized into bare nuclei
and free electrons, even the nuclei themselves were "ionized"
into their constituent neutrons and protons. As the expansion of
the Universe cooled the plasma, neutrons and protons combined to
form bound states, i.e., nuclei. These were created via fusion
reactions, which first produced deuterium (the neutron-proton
bound state) and then the very stable helium-4 nucleus (which
consists of 2 protons and 2 neutrons). Big Bang nucleosynthesis
theory predicts that 3 minutes after the Big Bang, the light
element abundances were set at uniform levels across the cosmos.
-----------
Science 2001 294:529
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SCIENCE-WEEK 25 Jan 2002 http://scienceweek.com
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13. POSTDOCTORAL FELLOWSHIP PROFILE:
Laboratory of H.S. Bernstein, Univ. of California San Francisco
---------------------------------------------------------------
INSTALLATION: University of California San Francisco
DEPARTMENT: Cardiovascular Research Institute and UCSF
Cancer Center
GENERAL RESEARCH AREA: Molecular and Cellular Biology
HEAD OF THIS SPECIFIC LAB: Harold S. Bernstein, MD PhD
POSTDOCTORAL FELLOWSHIPS ARE AVAILABLE IN THE FOLLOWING
SPECIFIC RESEARCH PROBLEMS: Current projects focus on
signaling/gene transcription governing cardiomyocyte
proliferation and differentiation. Systems include primary
cell culture and mouse models.
PREVIOUS RESEARCH EXPERIENCE AND DEGREES REQUIRED:
Applicants must have PhD and/or MD; strong background in
molecular/cellular biology. Experience in gene targeting and
transgenic mouse work highly sought.
USUAL STARTING STIPEND: Commensurate with NIH pay scale for
postgraduate training.
SPECIAL REQUIREMENTS: US citizenship/permanent residency
required.
APPROXIMATELY NUMBER OF PEOPLE CURRENTLY WORKING IN THIS
SPECIFIC LABORATORY (FACULTY, STAFF, STUDENTS, POSTDOCS): 10
1 Principal Investigator (faculty)
1 Senior research associate
1 Junior research associate
5 Postdoctoral fellows (3 PhD, 2 MD)
1 Pre-doctoral student
1 Administrative assistant
CONTACT FOR MORE INFORMATION: Send curriculum vitae,
research summary, and names of three references to:
H.S. Bernstein, MD, PhD, University of California, San Francisco,
505 Parnassus Ave., Box 0130, San Francisco, CA 94143-0130. Fax
415-514-0235; E-mail: hsbernstein@pedcard.ucsf.edu. Internet:
http://bernstein.ucsf.edu. Please do not contact by telephone.
FURTHER RELEVANT INFORMATION: UCSF is an Affirmative Action/
Equal Opportunity employer.
--------------------------------------------------------------
Please note: Postdoctoral Fellowship Profiles are provided to
ScienceWeek by the heads of laboratories, and ScienceWeek does
not charge for their publication. For information about
publishing a Postdoctoral Fellowship Profile, contact Claire
Haller at haller@scienceweek.com
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14. IN FOCUS: ON CONTINENTAL DRIFT AND PLATE TECTONICS
"Since the 16th century, cartographers have noticed the jigsaw-
puzzle fit of the continental edges. Since the 19th century,
geologists have known that some fossil plants and animals are
extraordinarily similar across the globe, and some sequences of
rock formations in distant continents are also strikingly alike.
At the turn of the 20th century, Austrian geologist Eduard Suess
[1831-1914] proposed the theory of Gondwanaland to account for
these similarities: that a giant supercontinent had once covered
much or all of the Earth's surface before breaking apart to form
continents and ocean basins. A few years later, German
meteorologist Alfred Wegener [1880-1930] suggested an alternative
explanation: continental drift. The paleontological patterns and
jigsaw-puzzle fit could be explained if the continents had
migrated across the Earth's surface, sometimes joining together,
sometimes breaking apart. Wegener argued that for several hundred
million years during the late Paleozoic and Mesozoic eras (200
million to 300 million years ago), the continents were united
into a supercontinent that he labeled _Pangea_ -- all Earth.
Continental drift would also explain paleoclimate change, as
continents drifted through different climate zones and ocean
circulation was altered by the changing distribution of land and
sea, while the interactions of rifting and drifting land masses
provided a mechanism for the origins of mountains, volcanoes, and
earthquakes. Continental drift was not accepted when first
proposed, but in the 1960s it became a cornerstone of the new
global theory of plate tectonics. The motion of land masses is
now explained as a consequence of moving 'plates' -- large
fragments of the Earth's surface layer in which the continents
are embedded."
-----------
Naomi Oreskes (ed.): _Plate Tectonics: An Insider's History of
the Modern Theory of the Earth_
(Westview Press, Cambridge MA 2001, p.3)
http://www.amazon.com/exec/obidos/ASIN/0813339812/scienceweek
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15. FROM PRAXIS:
ON THE ETIOLOGY OF PARKINSON DISEASE
W.K. Scott et al (Duke University, US) discuss the etiology of
Parkinson disease (also called Parkinson's disease), the authors
making the following points:
1) Parkinson disease is a neurodegenerative disease that
affects more than 500,000 people in the US, and the economic,
social, and emotional burden of this disease will increase as the
population ages.
2) Controversy has surrounded the etiology of Parkinson
disease, with evidence suggesting that both genetic and
environmental factors influence disease risk. Familial
aggregation of Parkinson disease has been observed for decades,
and data from family studies, including a recent large study from
Iceland, have shown that the sibling recurrence ratio ranges from
2 to 10, suggesting that a genetic component to Parkinson disease
exists. However, twin studies have produced conflicting results
concerning the genetic contributions, suggesting that little if
any genetic contribution exists in the development of Parkinson
disease.
3) The authors carried out what is apparently the largest
complete genomic screen in idiopathic Parkinson disease. The
authors suggest that the results provide strong evidence that the
parkin gene is influential in the development of early-onset
Parkinson disease, that several genes may influence the
development of late-onset Parkinson disease, and that age at
onset and levodopa response pattern may be useful discriminators
for genetic etiology. "Like many complex traits, it is likely
that Parkinson disease is caused by an interaction of genetic and
environmental risk factors, in which specific genetic templates
are more susceptible to the influences of environmental
exposures."
-----------
J. Am. Med. Assoc. 2001 286:2239
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PRAXIS 21 Jan 2002 http://scienceweek.com/praxis
----------
Related Background:
THE ENVIRONMENT AND PARKINSON'S DISEASE
Bette Hileman (CEN) discusses the relation between Parkinson's
disease and the environment. Parkinson's disease is a progressive
and incurable disorder, and the second most common
neurodegenerative disease in the US. The disease begins when a
class of brain cells that produce *dopamine start to die,
symptoms becoming apparent only when 60 to 80 percent of these
cells are dead. The disease is characterized by resting tremor,
rigidity, slow movement, postural instability, and progressively
involuntary writhing movements, paralysis, and an inability to
talk or even swallow. Although the medication levodopa, a
dopamine precursor, relieves many symptoms of the disease, the
effectiveness of the medication declines as the disease
progresses. Only approximately 10 percent of cases of Parkinson's
disease are familial, i.e., apparently caused by inherited
dysfunction. The remainder of cases apparently result from
unknown factors that include an interaction between genetic
susceptibility and the environment. Essentially 3 lines of
evidence have led researchers to believe that chemical exposures,
particularly to pesticides, play a role in some cases of
Parkinson's disease: a) people who live in farming areas,
especially those who drink well water, and who have a history of
exposure to pesticides, are more likely to contract the disease;
b) several studies have demonstrated that those who die of the
disease have higher levels of organochlorine pesticides in their
brains than the general population; c) in the early 1980s, a
group of young people developed Parkinson's disease after taking
illegal drugs containing a contaminant (MPTP), a substance whose
metabolite is similar to the pesticide paraquat.
-----------
Chem. & Eng. News 2001 17 Sep
-----------
Notes:
... ... *dopamine: Dopamine is an important neurotransmitter in
the human brain, and it has been implicated in several serious
behavioral pathologies. There is a dopamine hypothesis of
depression, a dopamine hypothesis of schizophrenia, and dopamine
has also been implicated in the reinforcing effects of
psychostimulant drugs of abuse such as cocaine and amphetamine.
-----------
PRAXIS 22 Oct 2001 http://scienceweek.com/praxis
-------------------
Related Background:
LINK BETWEEN HOME PESTICIDE EXPOSURE AND PARKINSON'S DISEASE
Parkinson's disease (also called Parkinson disease) is a
slowly progressive degenerative central nervous system disorder
characterized by decreased movement, muscular rigidity, resting
tremor, and postural instability. The disease was first described
by James Parkinson in 1817 and is now known to be associated with
degeneration of one or more specific regions of the brain
(dopaminergic neuron groups) and resultant loss of neural
connections (projections) from these groups to several important
brain centers. Dopaminergic neurons are nerve cells that use
dopamine as a *neurotransmitter substance. Dopamine is found in
several major areas of the brain, and it is the degeneration of
so-called dopamine neurons that is apparently involved in
Parkinson's disease.
One must distinguish "parkinsonism" from Parkinson's
disease. Parkinsonism is a syndrome (a complex of symptoms; in
this context, a complex of various movement symptoms) that may be
caused by Parkinson's disease, but which may also be caused by
infectious, vascular, pharmacological, toxic, metabolic,
structural, and various degenerative disorders. In other words,
not every individual with parkinsonism has Parkinson's disease.
The major differentiating characteristic is the response to the
drug "*levodopa", which is converted by the body into dopamine.
Individuals with parkinsonism who respond to levodopa treatment
receive a diagnosis of Parkinson's disease. At the present time,
Parkinson's disease is the 4th most common neurodegenerative
disease of the elderly. It affects approximately 1 percent of
people older than 65 years, and 0.4 percent of people between 40
and 65 years.
... ... Joan Stephenson (J. Amer. Med. Assoc., US) reviews a
presentation by Lorene Nelson (Stanford University) at a recent
meeting of the American Academy of Neurology, at which meeting
Nelson presented evidence of a link between home pesticide use
and Parkinson's disease. Stephenson makes the following points:
1) The study involved 496 patients diagnosed with
Parkinson's disease within the Kaiser Permanente Medical Care
Program of Northern California during the years 1994-1995, and
541 age- and sex-matched controls from the same population. Using
in-person structured interviews, a research team collected
information about lifetime history of exposure to home pesticides
(herbicides, insecticides, and fungicides) prior to diagnosis.
2) After controlling for known risk factors such as family
history of the disorder, occupational exposure to pesticides and
herbicides, and cigarette smoking, the investigators found that
home exposure to insecticides and herbicides were associated with
an increased risk of Parkinson's disease. Fungicide exposure was
not linked with an increased risk of the disorder.
3) Individuals with high-level herbicide exposure had a 70
percent increased risk compared with those who were not exposed.
People who used insecticides in the garden showed a 50 percent
increased risk compared to those who had never been exposed to
home pesticides of any type. In-home use of insect-killing
chemicals was associated with a 70 percent increased risk of
Parkinson's disease compared with no use of pesticide.
4) In her report to the American Academy of Neurology,
Lorene Nelson, a neuroepidemiologist, pointed out that the idea
that pesticides might be linked with Parkinson's disease is
biologically plausible, since many pesticides are neurotoxic and
may affect various aspects of central nervous system function,
possibly even resulting in the death of specific nerve cells.
Previous studies have found a substantially increased rate of
Parkinson's disease among city dwellers who gardened for a hobby.
-----------
J. Am. Med. Assoc. 2000 283:3055
-----------
Notes:
... ... *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.
... ... *levodopa: (L-dopa) The biologically active form of
"dopa", which is converted into dopamine. Dopamine = 3,4-
dihydroxyphenylethylamine. Dopa = 3,4-dihydroxypheynylalanine.
-----------
ScienceWeek 2000 18 Aug
-----------
PRAXIS 22 Oct 2001 http://scienceweek.com/praxis
----------
Related Background:
MEDICAL BIOLOGY: GENETIC COMPONENTS IN PARKINSON'S DISEASE
... The disease has an early-onset form (age =< 50 years), and a
childhood form (juvenile Parkinson's disease), but most cases are
adult onset, with incidence increasing markedly past age 50
years.
The causes of Parkinson's disease are largely unknown, but
there is evidence that the disease has a genetic component. In a
few large families with early onset Parkinson's disease or
juvenile Parkinson's disease, the disease is transmitted as an
autosomal dominant or recessive trait resulting from mutations in
the genes encoding the proteins alpha-synuclein and parkin,
respectively. However, in the majority of families affected by
Parkinson's disease, the disease appears to skip generations,
irrespective of the age of onset. Therefore, this disease is
considered a complex, multifactorial disease resulting from
interaction between one or more genes and the environment.
... ... S. Sveinbjoernsdoettir et al (9 authors at 2
installations, IS US) report a study of familial aggregation of
Parkinson's disease in Iceland, the authors making the following
points:
1) The authors reviewed the medical records and confirmed
the diagnosis of Parkinson's disease in 772 living and deceased
patients in whom the disease had been diagnosed during the
previous 50 years in Iceland. With the use of an extensive
computerized database containing genealogical information on
610,920 people in Iceland during the past 11 centuries, several
analyses were conducted to determine whether the patients were
more related to each other than random members of the population
(the control subjects).
2) Patients with Parkinson's disease, including a subgroup
of 560 patients with late-onset disease, were significantly more
related to each other than were subjects in matched groups of
controls, and this relatedness extended beyond the nuclear
family. The risk ratio for Parkinson's disease was 6.7 for
siblings, 3.2 for offspring, and 2.7 for nephews and nieces of
patients with late-onset Parkinson's disease.
3) In summary, the authors suggest late-onset Parkinson's
disease has a genetic component as well as an environmental
component. The authors conclude: "There has been a recent trend
to discount the possibility that genetic factors contribute to
the late-onset form of the disease, which represents the majority
of cases of Parkinson's disease. Although the search for
environmental factors contributing to late-onset Parkinson's
disease is important and should continue, our data suggest that
the search to discover its genetic basis should also continue."
-----------
New Engl. J. Med. 2000 343:1765
SCIENCE-WEEK 2000 15 Dec
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PRAXIS 21 Jan 2002 http://scienceweek.com/praxis
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SCIENCE-WEEK 25 Jan 2002 http://scienceweek.com
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16. THIS WEEK IN PRAXIS (21 Jan 02):
-------------------------------
1. On Contacts in Single-Molecule Electronics
2. Measurement of Single-Molecule Conductivity
3. Using Xenon as a Biosensor
4. On the Solubility of Fullerenes
5. Physics in a New Era
6. On Spin and Spintronics
7. Molecular Testing for Infectious Disease
8. Implications of Genome Research for Human Biology and Medicine
9. Impact of Tropical Lowland Deforestation
10. On the Etiology of Parkinson Disease
11. On Biochips
12. Cardiac Arrhythmias and Sudden Death
For information about PRAXIS, see:
http://www.scienceweek.com/praxis
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In the text, the affiliation following the names of authors is
the affiliation of the lead author.
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