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ScienceWeek
SCIENCE-WEEK
A Weekly Email Digest of the News of Science
A journal devoted to the improvement of communication
between the scientific disciplines, and between scientists,
science educators, and science policy-makers.
November 16, 2001 -- Vol. 5 Number 46
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Here is a biologist examining a culture of nerve
cells in a small dish. One set of nerve cells
examining another set of nerve cells. Not quite
a trivial scenario.
-- Unknown
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Section 1
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Contents of this Issue (Full reports in Section 2):
1. DNA Instability and Neurodegenerative Diseases
2. On the Intracellular Symbiotic Bacterium Wollbachia
3. Amino Acids and Protein Folding
4. On Catalases in Biological Systems
5. On the Coding Capacity of the Human Genome
6. Adaptation and Neural Codes
7. Supramolecular Chemistry
8. On Cation-Pi Electron Interactions in Proteins
9. Comparative Geology of Earth and Mars
10. On the Composition of the Moon
11. Hydrogen Markers in Astrophysics
12. On the Chemistry and Biology of Strychnine
13. In Focus: On the Treatment of the Mentally Ill in 18th
Century America
14. From PRAXIS: Relation Between Depression and Other Medical
Illnesses
15. Sources
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Section 2
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1. DNA INSTABILITY AND NEURODEGENERATIVE DISEASES
Richard R. Sinden (Texas A & M University, US) discusses errors
in DNA replication and neurodegenerative diseases. Many
neurological and neurodegenerative diseases, such as
*Huntington's disease and *fragile X syndrome, share a similar
apparent genetic basis -- the lengthening of tracts of repeated
DNA sequence. The molecular mechanisms that cause this "repeat
instability" have attracted much attention but have remained
elusive. Currently, however, there is some excitement among
researchers concerning new evidence that proteins that repair
damaged DNA may be responsible for generating repeat instability
in cells that are not dividing. At least 14 human diseases have
been associated with the lengthening (expansion) of tracts of
nucleotide triplets in various human genes. As well as
Huntington's disease and fragile X syndrome, these diseases
include *myotonic dystrophy type 1, several *spinocerebellar
ataxias, and *Friedreich's ataxia. The pathological bases of
these diseases vary, but DNA repeat expansion is the underlying
mutation in all of them. Two principal classes of repeat
instability are associated with these diseases: 1) When the
tracts of repeats occur within non-protein-coding regions of an
affected gene, the tracts can expand by a factor of 10 to 20, or
even more, between generations. This large-scale expansion occurs
in fragile X syndrome, myotonic dystrophy, certain
spinocerebellar ataxias, and Friedreich's ataxia. 2) Small-scale
expansion of cytosine-adenine-guanine (CAG) repeats can cause
disease when the repeats encode a tract of polyglutamine amino
acids within an affected protein. For example, the presence of 30
CAG repeats in the gene encoding the huntingtin protein is in the
normal range, whereas more than 36 CAG repeats cause Huntington's
disease.
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NAT 2001 411:757
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Notes:
... ... *Huntington's disease: (Huntington's chorea) First
described by George Huntington (1850-1916), the disease attacks
specific regions of the brain (e.g., caudate nucleus and
putamen), and leads to insanity and eventual death.
... ... *fragile X syndrome: An chromosome X-linked recessive
syndrome with mental retardation as the most important
characteristic. The incidence is approximately 1 in 2000, which
makes it second only to Down syndrome among genetically
identifiable sources of mental retardation.
... ... *myotonic dystrophy type 1: Myotonic dystrophy
(Steinert's disease) is the most common adult muscular disorder,
characterized by progressive muscle weakness and wasting. The
genetic defect has been localized to the long arm of chromosome
19.
... ... *spinocerebellar ataxias: In general, an ataxia is an
inability to coordinate muscle activity during voluntary
movement. Spinocerebellar ataxia is the most common hereditary
ataxia. The spinocerebellar degenerative disorders are a group of
diseases involving neurons in several nervous system structures,
including the spinal cord and cerebellum.
... ... *Friedreich's ataxia: A spinal ataxia due to a mutation
on chromosome 9. Gait unsteadiness usually begins between the
ages of 5 and 15 years.
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Related Background:
ON THE MOLECULAR BASIS OF THE NEURODEGENERATIVE DISEASES
The term "neurodegenerative disorders" is loosely applied to a
group of chronic and progressive diseases of the nervous system,
all of which are characterized by selective and symmetric loss of
neurons in motor, sensory, or cognitive systems. Some
neurodegenerative diseases are extremely cell-specific, causing
loss of only one type of nerve cell, while the neuronal loss
caused by other neurodegenerative diseases is more general,
affecting a wide variety of nerve cells. In all cases, these
diseases primarily affect nerve cells and not other cells.
... ... Joseph B. Martin (Harvard University, US) presents a
review of the molecular basis of neurodegenerative disorders, the
author making the following points:
1) Delineation of the patterns of cell loss and
identification of disease-specific cellular markers have aided in
the classification of these diseases. For example:
... ... a) *Alzheimer's disease is characterized by *senile
plaques, *neurofibrillary tangles, neuronal loss, and
*acetylcholine deficiency.
... ... b) *Parkinson's disease is characterized by *Lewy bodies
and depletion of *dopamine.
... ... c) *Amyotrophic lateral sclerosis is characterized by
*cellular inclusions and swollen *motor axons.
... ... d) *Huntington's disease is characterized by loss of
*gamma-aminobutyric acid-containing neurons of the *neostriatum.
2) *Mendelian inheritance can be demonstrated in many
neurodegenerative disorders. In some diseases, such as
Huntington's disease, a family history of the disease can be
ascertained in almost every case, whereas in other diseases, such
as Alzheimer's disease, Parkinson's disease, and amyotrophic
lateral sclerosis, about 1 to 10 percent of cases are inherited.
In other conditions, such as *spinocerebellar ataxia, the
syndromes have been difficult to classify because of clinical
overlap, and variants can only be differentiated by genotyping
after the mutant genes have been identified.
3) In families with the above and other neurodegenerative
disorders, *linkage analysis, *positional cloning, and searches
for mutations in candidate genes have been extremely productive.
These efforts, which began in the 1980s with the search for the
gene that causes Huntington's disease, have led to the
identification of mutant genes in more than 50 disorders of the
nervous system.
4) The genetic anomalies that cause neurodegenerative
diseases are varied and complex. In some diseases, several genes
have been found, each of which leads to a similar clinical and
pathological syndrome, with only variations in the age at onset
and the rate of progression to suggest that there are differences
in pathogenic mechanisms. In other disorders, errors in DNA
replication resulting in an increased number of *nucleotide
triplet repeats are associated with selective patterns of
neurodegeneration.
5) In general, the various pathologies of the
neurodegenerative disorders apparently involve abnormalities in
the transport, degradation, and aggregation of proteins that lead
to cell-specific changes and ultimately to neuronal death,
probably by *apoptosis.
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NEJM 1999 340:1970
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Notes:
... ... *Alzheimer's disease: Alzheimer's disease is
characterized by the presence of large numbers of extracellular
agglomerations (plaques) and intracellular *neurofibril tangles
in the cerebral cortex of the brain. There is also a massive
neuronal cell loss. While plaques and tangles are found in normal
aging brains, they are more numerous and widespread in
Alzheimer's disease. The major protein component of the plaques
is a 39 to 43 amino acid peptide called beta-amyloid, which is
now known to be derived from a much larger protein called the
amyloid precursor protein. This latter protein has been found to
be expressed in every tissue studied.
... ... *neurofibril: A filamentous structure seen with the light
microscope and composed of ultramicroscopic tubular and
filamentous protein arrays (neurotubules and microfilaments). The
function of these structures is unknown.
... ... *senile plaques: In general, the term "plaque" refers to
a deposit. In this context, the deposits are usually
extracellular protein agglomerations.
... ... *neurofibrillary tangles: A neurofibril is a filamentous
structure seen with the light microscope and composed of
ultramicroscopic tubular and filamentous protein arrays
(neurotubules and microfilaments). The function of these
structures is unknown.
... ... *acetylcholine: In general, a neuron has input extensions
(dendrites) and a single but usually branched output extension
(axon). The junction between the terminal of a neuron's axon and
another neuron is called a "synapse". When studying the synapse,
the first neuron is called the "presynaptic" neuron, and the
second neuron is called the "postsynaptic" neuron.
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. At present acetylcholine, 5 amines, 4 amino acids, 2
purines, and more than 28 peptides are known to be
neurotransmitters.
... ... *Parkinson's disease: A neurological disorder first
described by James Parkinson (1817) and associated with
degeneration of a specific small region of the brain and a
resultant loss of projection to several important brain centers.
... ... *Lewy bodies: Intracytoplasmic neuron inclusions
especially seen in Parkinson's disease.
... ... *dopamine: 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.
... ... *Amyotrophic lateral sclerosis: A progressive disease of
motor neurons (spinal cord nerve cells that control voluntary
muscles). 50 percent of patients die within 3 years of the first
symptoms.
... ... *cellular inclusions: A general term for residual
entities in cytoplasm produced by metabolism; in this context,
granules or crystals not found in normal cells.
... ... *motor axons: Axons of motor neurons. They can be quite
long: a spinal cord motor neuron controlling muscles in a toe,
for example, has a cell body in the spinal cord and an axon that
runs as a single extension from the spinal cord down to the toe
musculature. Such axons usually propagate impulses at high
velocity (e.g., 100 meters per second).
... ... *Huntington's disease: (Huntington's chorea) First
described by George Huntington (1850-1916), the disease attacks
specific regions of the brain (e.g., caudate nucleus and
putamen), and leads to insanity and eventual death.
... ... *gamma-aminobutyric acid: A widely distributed brain
neurotransmitter.
... ... *neostriatum: This is a term used when considering the
two brain regions, the caudate nucleus and the putamen, as a
single anatomical entity.
... ... *Mendelian inheritance: In general, any inheritance
scenario following the classical Mendelian laws governing the
inheritance of chromosomal genes via the transmission of
chromosomes to subsequent generations, and producing inheritance
of single-chromosome-locus traits.
... ... *spinocerebellar ataxia: In general, an ataxia is an
inability to coordinate muscle activity during voluntary
movement. Spinocerebellar ataxia is the most common hereditary
ataxia. The spinocerebellar degenerative disorders are a group of
diseases involving neurons in several nervous system structures,
including the spinal cord and cerebellum.
... ... *linkage analysis: In general, an analysis of chromosomal
gene location based upon inheritance patterns.
... ... *positional cloning: In general, the identification of a
gene responsible for a disease from a knowledge of its position
in the human genome, and no assumptions about the gene product.
Inherited disease genes identified by positional cloning include
Duchenne muscular dystrophy and Huntington's disease.
... ... *nucleotide triplet repeats: (coding triplet repeats;
codon repeats) In general, a codon is the basic genetic
coding unit, a triplet of nucleotides in DNA. A codon repeat is a
string of identical codons which if expressed produce a string of
identical amino acids in a protein.
... ... *apoptosis: In general, programmed cell death produced by
control mechanisms designed to destroy defective cells.
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SW 1999 2 Jul
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Related Background:
NEURODEGENERATIVE DISEASE AND SPECIFIC MEMBRANE ION CHANNELS
There are a number of human neurodegenerative diseases that
involve the destruction of specific types of nerve cells, rather
than nerve cells in general (amyotrophic lateral sclerosis, for
example), but the mechanisms for the specificity and the eventual
death of the nerve cells is not known. It has been suggested that
specific gene mutations leading to aberrant ion channels may be
involved. Now Jian Zuo et al (Rockefeller University, US; Johns
Hopkins University, US) report studies of "lurcher" mice, a
mutant that exhibits ataxia associated with death of Purkinje
cells in the cerebellum. What they find is that the mutants have
aberrant glutamate neurotransmitter receptors, which in turn may
result in excess concentrations of calcium ions, enough
intracellular calcium ions to lead to cell death.
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NAT 1997
SW 1997 29 Aug
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2. ON THE INTRACELLULAR SYMBIOTIC BACTERIUM WOLLBACHIA
F. Dedeine et al (CNRS Lyon, FR) discuss *symbiotic Wollbachia
bacteria. Wollbachia are strictly intracellular bacteria
infecting a number of invertebrates, including mites,
crustaceans, filarial nematodes (a class of parasitic
roundworms), and especially insects, in which 16 percent of
species can be infected. Wollbachia are maternally transmitted
via the cytoplasm of eggs, and are of special interest in the
study of the evolution of symbiosis because they would seem not
to fit current theory that vertically transmitted microorganisms
(i.e., transmitted from parent to offspring) tend to evolve
toward a benign state or a state where they are beneficial to
their hosts. In invertebrates, Wollbachia cause a wide range of
effects on physiology and reproduction. The authors investigated
the effect of Wollbachia infection in the parasitic wasp Asobara
tabida. In the 13 populations tested, all individuals proved to
be infected by Wollbachia. The removal of Wollbachia by
antibiotic treatment had a totally unexpected effect -- female
wasps were completely incapable of producing mature egg cells
(oocytes) and therefore could not reproduce. In contrast,
oogenesis was not affected in treated Asobara citri, a closely
related species that does not harbor Wollbachia. This and other
evidence leads the authors to conclude that Wollbachia is
necessary for oogenesis in these A. tabida strains, and this
association would seem to be the first example of a transition
from *facultative to obligatory symbiosis in arthropod-Wollbachia
associations.
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PNAS 2001 98:6247
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Notes:
... ... *symbiotic: In biology, symbiosis is an intimate and
protracted association of individuals of different species.
Mutualism is a type of symbiosis in which both participants
receive benefits from the association.
... ... *facultative: A "facultative symbiont" is a symbiont also
capable of surviving in a free-living state.
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3. AMINO ACIDS AND PROTEIN FOLDING
R. Schweitzer-Stenner et al (University of Puerto Rico, PR)
discuss protein folding. A thorough understanding of protein
folding is still one of the major topics of contemporary
biochemistry and structural biology. Three of the open questions
refer to the early phase of the folding process, which leads to
the formation of *secondary structure motifs: 1) How many amino
acids are necessary to allow for the formation of a stable
conformation in aqueous solution? 2) What are the optimum
compositions with respect to the most prominent types of
secondary structures? 3) What are the structures of segments
constituting the initial step of secondary structure formation
and how do they depend on the amino acid composition? Numerous
studies have been made to identify the propensity of the 20
naturally proteinogenic amino acids for one of the natural
abundant secondary structures, and these studies were then used
as a basis for secondary structure prediction. Chou and Fasman
(1978) undertook a statistical survey of the crystal structures
of 15 proteins to obtain conformational parameters for all amino
acid residues, which were used as a measure of their respective
propensities. All these studies agree in pointing to alanine as a
strong helix former, and this is supported by the fact that short
(16 to 20 member) alanine-based peptides were found to form
stable alpha-helices in water. Studies on these peptides also
reveal that charged side chains can stabilize helical
conformations, particularly if they are positioned close to the
terminal groups of the protein.
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JACS 123:9628
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Notes:
... ... *secondary structure: In general, the structures of
biopolymers are denoted as follows: 1) Primary structure: The
sequence of subunits that comprise the macromolecule (e.g., the
amino acid sequence of a protein). 2) Secondary structure: The
localized arrangement in space of regions of a biopolymer (e.g.,
the alpha-helix). 3) Tertiary structure: The 3-dimensional
configuration of a biopolymer. 4) Quaternary structure: The
3-dimensional arrangement and constitution of a multimeric
macromolecule (i.e., a substance containing more than one
biopolymer; an entity consisting of biopolymer subunits.
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Related Background:
BIOCHEMISTRY: ON PROTEIN FOLDS AS NATURAL FORMS
Proteins are polymers consisting of long chains of amino
acid residues, but that is only the beginning of their functional
chemistry. In biological systems, proteins assume various complex
high-order configurations ("folding"), and it is these
configurations that usually determine the roles of proteins as
biochemical entities in the biological system. An important goal
of molecular biology is to understand the structural and
functional features of proteins, in particular the mechanisms
responsible for specific protein folding.
The term "alpha helix" refers to a spiral configuration of a
polypeptide chain in which successive turns of the helix are held
together by hydrogen bonds between the amide (peptide) links, the
carbonyl group of any given residue being hydrogen-bonded to the
imino group of the 3rd residue behind it in the chain. The term
"beta sheet" (beta-pleated sheet) refers to an array of two or
more "beta strands", with each beta strand consisting of two
polypeptide chains in a so-called "beta configuration", which in
turn is a stable configuration of a polypeptide chain in which
the chain is almost fully extended and hydrogen-bonded to an
adjacent polypeptide chain.
In this context, the term "natural forms" refers to forms
that are an apparent intrinsic part of the natural order of the
world, for example, inorganic forms such as atoms or crystals.
... ... M. Denton and C. Marshall (University of Otago, NZ)
present an essay on protein folds as natural forms, the authors
making the following points:
1) The authors point out that a protein fold consists of a
folded chain of between 80 and 200 amino acids, with some
proteins possessing a single fold, but most proteins having a
combination of two or more folds. During the 1970s, as the 3-
dimensional structure of an increasing number of folds was
determined, it became apparent that the folds could be classified
into a finite number of distinct structural families containing a
number of closely related forms. The fact that protein folds
could be classified in this manner provided the first line of
evidence that the folds might be natural forms.
2) The authors point out that further evidence that protein
folds do indeed represent a finite set of natural forms is
provided by detailed structural studies during the past two
decades, these studies revealing that the structure of protein
folds can be accounted for by a set of "constructional rules"
that govern the manner in which the various secondary structural
motifs, such a alpha-helices and beta-sheets, can be combined and
packed into compact 3-dimensional structures.
3) The authors suggest that considerations of these
"constructional laws" indicates that the total number of
permissible protein folds is bound to be restricted to a very
small number -- approximately 4000, according to one estimate.
Other estimates suggest the total number of protein folds used by
living organisms may not be more than 1000. The authors state:
"Whatever the final figure, the fact that the total number of
folds represents a tiny stable fraction of all possible
polypeptide conformations, determined by the laws of physics,
reinforces the notion that the folds, like atoms, represent a
finite set of built-in natural forms."
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NAT 2001 410:417
SW 2001 25 May
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Related Background:
MOLECULAR BIOLOGY: NATURAL HISTORY AND PROTEIN FOLDING
Although the term "evolution" is usually applied to the natural
history of entire organisms, another perspective is to consider
the evolution of biological molecules, particularly the protein
biomolecules. The proteins of an organism, the end products of
the working of genes, evolve just as genes evolve, and an
important question is how knowledge of the evolution of proteins
can be used to understand protein dynamics.
... ... Steven A. Benner (University of Florida, US) presents an
essay on the natural history of biomolecules, the author making
the following points concerning natural history and protein
folding:
1) The author suggests that many chemical biologists and
biophysicists view the future of biology as a metamorphosis in
which understanding of biological phenomena will be replaced by
understanding of the interactions of their underlying
physicochemical components. This metamorphosis is already ongoing
and very productive, but it is unlikely to be the entire story.
The author suggests the surprise will come when biophysicists and
chemical biologists discover that they need to research the
history of biomolecules if they are to understand the physical
behaviors they are attempting to characterize.
2) One example of the need for natural history is the
problem of protein folding. Physical chemists have mounted a
frontal assault on this problem, using computers to build
physical models of proteins in water, the models involving
guesses concerning many aspects of atomic interactions. The
assault has failed. The only way to make such a computation even
vaguely tractable requires considerable abstraction of the
physical model for the protein, and the same physical theory that
inspired the computation indicates that these abstractions must
compromise the value of the computation as a predictive tool.
3) Natural history offers an entirely different approach to
protein folding. Divergent evolution creates families of proteins
that have descended from common ancestors. As proteins evolve
from these ancestors, natural selection requires them to remain
"fit". The principal prerequisite for fitness in a protein is a
particular folding of the protein, so proteins that diverge from
a common ancestor generally conserve their folds. This means that
during the evolution of protein sequences, mutations do not
accumulate as they would if proteins were formless and
functionless organic molecules. Instead, amino acids that are
important to the fold experience substitution differently from
those amino acids that are not important to the fold. A signal
should lie in the pattern of protein-sequence divergence -- the
difference between how proteins have divergently evolved in the
past, and they would have evolved had they been formless and
functionless molecules.
4) At present, the *secondary and tertiary structure of
proteins can reliably be predicted by exploiting the historical
signal embedded in a set of protein sequences related by common
ancestry. Since 1990, approximately 30 protein folds have been
predicted using the history of protein families. In many cases,
the prediction provided information about the function as well as
about the form of the protein.
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NAT 2001 409:459
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Notes:
... ... *secondary and tertiary structure: In general, the
structures of biopolymers are denoted as follows: 1) Primary
structure: The sequence of subunits that comprise the
macromolecule (e.g., the amino acid sequence of a protein). 2)
Secondary structure: The localized arrangement in space of
regions of a biopolymer (e.g., the alpha-helix). 3) Tertiary
structure: The 3-dimensional configuration of a biopolymer. 4)
Quaternary structure: The 3-dimensional arrangement and
constitution of a multimeric macromolecule (i.e., a substance
containing more than one biopolymer; an entity consisting of
biopolymer subunits. (Also, see related background material
below.)
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SW 2001 9 Feb
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Related Background:
BIOCHEMISTRY: PHYSICAL BASIS FOR PROTEIN SECONDARY STRUCTURE
The term "protein" was first used by the chemist Gerardus
Mulder (1802-1880) to denote the basic building block of the heat
coagulable (albuminous) material found in living systems, but it
was not until the 1920s that proteins were generally recognized
as a special type of macromolecule (a polypeptide) and studied as
polymers. Currently, biochemists and protein chemists distinguish
four orders of polymeric structure in proteins:
1) The term "primary" structure refers to the linear
structure of the polypeptide as determined solely by the number,
sequence, and type of amino acid residues.
2) The "secondary structure" of a protein is determined by
interactions between the sequential units, particularly hydrogen
bonding between particular amino acids and nonpolar interactions
between hydrophobic regions, the interactions producing, in
general, three local or global secondary structure variants:
alpha helix, beta sheet, and tight turn. An "alpha helix" is a
spiral configuration of a polypeptide chain in which successive
turns of the helix are held together by hydrogen bonds between
the amide (peptide) links, the carbonyl group of any given
residue being hydrogen-bonded to the imino group of the 3rd
residue behind it in the chain. The term "beta sheet" (beta-
pleated sheet) refers to an array of two or more "beta strands",
with each beta strand consisting of two polypeptide chains in a
so-called "beta configuration", which in turn is a stable
configuration of a polypeptide chain in which the chain is almost
fully extended and hydrogen-bonded to an adjacent polypeptide
chain. The third secondary structure variant, "tight turn" (beta
bend; beta turn) refers to a bending of a short stretch of
polypeptide chain that allows the main direction of the chain to
change. The turn consists of 4 amino acid residues in which the
CO group of residue n is hydrogen-bonded to the NH group of
residue n + 3.
3) The "tertiary structure" of a polypeptide is a 3-
dimensional configuration, a folding or coiling of the molecule
primarily determined by interactions of hydrophobic regions and
to a lesser extent by hydrogen bonding.
4) The "quaternary structure" of proteins is characterized
by the interaction of 2 or more individual polypeptides, often
via disulfide bonds, the result a larger functional molecule.
Although given the above rough categorization of protein
structures, there are many aspects that might be of interest,
there are two salient generalizations concerning proteins which
command attention: a) when, as the result of the expression of a
gene, a specific protein is synthesized in a living system, that
protein rapidly assumes a configuration specific for its type;
and b) whatever it is that a specific protein does in a living
system, that action is dependent primarily and directly on its
configuration rather than on its specific amino acid sequence.
These two generalizations form the basis for much of the research
on protein structure, with two resultant questions: a) What rules
govern the rapid folding into a particular configuration by a
protein? and b) How is the particular configuration of a protein
related to its biochemical actions in the living system? The
first question is currently viewed as a problem in the physical
chemistry of macromolecules, and research on the question has
been heavily theoretical, with models based on a wide range of
quantitative techniques.
The problem of protein folding is essentially as follows:
Given an ordinary polypeptide, the number of possible
configurations is astronomical. If a particular protein always
assumes the same configuration in a living system (its "native
configuration"), and if that configuration represents some sort
of energy minimum for the polypeptide chain, how does the protein
find that energy minimum within milliseconds? Does the protein
pass through every possible configuration state until the energy-
minimum configuration is "discovered"? Or are there constraints
that reduce the number of possible configurations to a much
smaller number? As easy as it is to state this problem, the
problem is a puzzle that has confounded researchers for 40 years.
... ... R. Srinivasan and G. Rose (Johns Hopkins University, US)
present a physical theory for protein secondary structure, the
authors making the following points:
1) The authors propose a physical theory for secondary
protein structure based on steric and local interactions, and
suggest their finding demonstrate that local, intrinsic,
sequence-dependent biases toward helix, strand, and turn
configurations are densely dispersed throughout the polypeptide
chain and are unlikely to be merely accidental. The authors
report tests of the theory by *Monte Carlo simulations.
2) The authors suggest that in essence, secondary structure
bias is largely a consequence of the balance between two opposing
local forces that govern the position of equilibrium between the
two mainchain states of contraction or extension. The competing
forces are attractive local interactions vs. sidechain
conformational restriction.
3) The authors point out that C.B. Anfinsen (1973) proposed
that proteins attain their native state by folding to a global
minimum of *Gibbs free energy, and that this hypothesis has
usually been interpreted to mean that the native conformation of
individual molecules also corresponds to a global minimum in
internal energy because a fully folded protein will have lost its
*conformational entropy, or almost so. Thus, conformational
entropy is thought to play an insignificant role in the
thermodynamics of protein folding. Specifically, the statistical-
mechanical- (Boltzmann-) weighted populations of any two states
are thought to depend predominantly on their energy difference.
In contrast, the work of the authors suggests the conclusion that
conformational entropy is the main factor that discriminates
between two energetically equivalent (degenerate) ground states,
and in so doing "preorganizes" the protein.
3) The authors point out that the problem of secondary
structure is intimately related to the Levinthal paradox [C.
Levinthal (1969)], which argues that a folding protein does not
"explore" conformational hyperspace freely; otherwise, the
protein would encounter an insoluble search problem. For
Levinthal, this insight was not a paradox at all, but a
convincing demonstration that some intrinsic constraint limits
the effective size of the conformational space. In this view,
proteins solve the "multiple-minimum problem" not by an extensive
search that identifies the deepest minimum, but by a limited
search that avoids false minima. The existence of intrinsic bias
resolves this paradox by prejudicing the ensemble of available
folding trajectories toward the native minimum. Thus, a folding
protein need not discriminate among an astronomical number of
conformations, because intrinsic bias "steers" the molecule
toward a high degree of preorganization. [*Note #1]
4) In summary, the authors suggest their analysis has
demonstrated that pronounced biases toward protein secondary
structure are present in natural protein sequences, that these
biases have a discernible physical basis, and that their
existence suggests reinterpretations of current folding models.
-----------
PNAS 1999 96:14258
-----------
Notes:
... ... *Monte Carlo simulations: In general, a "Monte Carlo
method" is any method for obtaining a statistical estimate of a
desired quantity by random sampling. In the most successful
applications, the desired quantity is a statistical parameter,
and the sampling is made from an artificial population that may
be a model of the physical system itself. The method is of
considerable utility in handling certain intractable applied
mathematical problems.
... ... *Gibbs free energy: (Gibbs function; thermodynamic
potential) A thermodynamic function of a system. In the present
context, if a system is considered at constant pressure and
temperature, and the only work done is that caused by changes in
volume, it can be shown that the system is in equilibrium when
the Gibbs free energy has a minimum value.
... ... *conformational entropy: In general, the entropy of a
system is a measure of the unavailability of its internal energy
to do work in a cyclic process. From the standpoint of
statistical mechanics, entropy is in general a measure of the
disorder of a system. The term "conformational entropy" refers to
that part of the total entropy of a system due to specific
orientations of atoms.
... ... *Note #1: In this paragraph, terms such as "hyperspace"
and "trajectory" derive from statistical mechanics and the
following considerations: If the state of a system depends upon N
variables, the state of the system can be viewed as a point
(phase point) in an N-dimensional space (phase space; system
hyperspace), and as the state of the system changes, its phase
point can be viewed as describing a trajectory in its phase
space. There are certain systems for which qualitative analysis
of the phase space trajectories of the system reveals significant
properties of the system otherwise difficult to delineate.
-------------------
SW 2000 28 Jan
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SCIENCE-WEEK 16 Nov 2001 http://scienceweek.com
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Related Background:
ON EXPLANATIONS OF PROTEIN FOLDING
Since the 3-dimensional configuration of a protein is an
essential determinant of what the protein does in a biological
system, protein "folding", the process that leads to this
configuration, is a central focus in biophysical chemistry.
... ... William A. Eaton (National Institutes of Health, US)
presents a review of current research in this field, the author
making the following points:
1) There are two aspects to the problem of protein folding.
The first is predicting the 3-dimensional structure of a protein
from its amino acid sequence; the second is to understand _how_
proteins fold. The problem of protein folding has recently
assumed additional importance as more and more human diseases
(e.g., Alzheimer's and Parkinson's diseases) are believed to be
caused by aggregation of misfolded proteins.
2) The question of _how_ a protein folds can be phrased more
precisely as follows: What are the sequences of structural
changes that occur in a polypeptide as it finds its way from the
myriad of possible structures in the *denatured state to the
final unique *native structure? How many different folding routes
exist, and what are their relative probabilities?
3) Until approximately a decade ago, the problem of
understanding how proteins fold was addressed by identifying and
characterizing one or two metastable structures believed to be
obligatory intermediates in a sequential process along a well-
defined protein-folding pathway. The prevailing view was that
structural characterization of such intermediates would give the
clue to the basic underlying mechanism, as in the study of
organic chemical reactions. However, unlike small-molecule
chemical reactions, in which covalent bonds are broken and new
bonds formed in a structurally well-defined transition state, the
many degrees of freedom of a polypeptide chain demand a different
approach. A polypeptide of 100 amino acids has a huge number of
conformations, even if only a tiny fraction of the more than
2^(100) (= 10^(30)) possible conformations are thermally
occupied. Understanding the complexities of protein folding at
the microscopic level, and developing models that make
quantitative predictions, therefore requires a statistical
approach, i.e., the theoretical and computational tools of modern
statistical mechanics.
4) Nonexponential kinetics have played an important role in
understanding conformational changes in native proteins. They are
particularly interesting for protein folding because they could
arise from a process that is "downhill" in free energy, i.e, one
in which the overall free energy barrier separating the native
from the denatured state is very small or nonexistent. For large
barriers, only the structures of the initial and final states are
observable, because structures along the folding route are too
sparsely populated. If, however, the barrier becomes very small
or disappears altogether, all of the structures can in principle
be detected and characterized by spectroscopy.
5) At the present time, there exists the exciting prospect
of performing single molecule experiments for direct exploration
of the energy landscape and folding routes. Finding proteins that
fold with a "downhill scenario" is an essential first step in
this quest. That some proteins will exhibit downhill folding,
moreover, is one of the novel theoretical predictions of an
energy landscape analysis of protein folding.
-----------
PNAS 1999 96:5897
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Notes:
... ... *denatured state: In biochemistry, the term
"denaturation" refers to the complete unfolding
and loss of catalytic activity of a protein.
... ... *native structure: The "native" structure or
configuration of a biological macromolecule is the functional
state or configuration ordinarily assumed by the molecule in the
biological system in which the molecule occurs.
-------------------
SW 1999 3 Sep
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Related Background:
PROTEIN FOLDING: ON OLEG PTITSYN (1929-1999)
... In recent decades, one of the leading personalities in the
field of protein folding was Oleg Ptitsyn (1929-1999). For nearly
30 years, Ptitsyn advocated the concept of the "molten globule"
as a key intermediate in protein folding. Ptitsyn's fundamental
idea that proteins can adopt compact structures without the
close-packed side-chain interactions characteristic of *native
proteins is now implicit in virtually every discussion of the
subject.
... ... C.M. Dobson and R.J. Ellis (2 installations, UK) present
a biographical essay on Oleg Ptitsyn, the authors making the
following points:
1) Ptitsyn was born in Leningrad in 1929, and he received a
doctorate in physics from the University of Leningrad at the age
of 25. His early work was on the physics of polymers at the
Institute of High Molecular Weight Compounds in Leningrad, but he
soon became interested in proteins and began work on protein
folding. With others, Ptitsyn founded the Institute of Protein
Research in Pushchino, a town approximately 70 miles from Moscow.
2) In the early 1970s, Ptitsyn speculated that the protein-
folding problem might be made much simpler if a polypeptide chain
folds first into a flexible state with the usual positioning of
*helices and sheets, but without the intricate and detailed
packing of the various side chains found in a fully native
protein. There was no experimental evidence for this proposal at
that time, but soon such evidence began to emerge from studies of
*protein denaturation in various laboratories.
3) Ptitsyn introduced the strategy of a combination of
physical methods to search for this new state of proteins. The
name "molten globule" was first used by Akiyoshi Wada in Japan.
The Ptitsyn laboratory subsequently made the major advance of
identifying species in kinetic experiments that fitted Ptitsyn's
definition of a molten globule, and then relating this state to
the mechanism of the folding process itself.
4) Concerning Ptitsyn the person, the authors write: "Oleg
Ptitsyn was a gentle, kindly person, whose diminutive and
bustling figure was familiar around the conference and lecture
halls of the world... He died on 22 March, just before he was due
to give a lecture at the University of Warwick, during one of his
frequent trips to Britain. It was as he would have wished. He
died, as he had lived, earnestly engaged in the practice of
science, and looking forward to intense discussions about his
latest ideas."
-----------
NAT 1999 400:122
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Notes:
... ... *native proteins: The "native" state or configuration of
a biological macromolecule is the functional state or
configuration ordinarily assumed by the molecule in the
biological system in which the molecule occurs.
... ... *helices and sheets: The "primary structure" of a
polypeptide chain is the actual sequence of amino acid residues;
the "secondary structure" is a low-order folding of the chain;
the "tertiary structure" is a high-order folding of the molecule.
Concerning the secondary structure, there are two main types: the
alpha configuration is a spiral configuration in which successive
turns of the helix are held together by hydrogen bonds; the beta
configuration is a configuration in which the chain is almost
fully extended and hydrogen bonded to an adjacent polypeptide
chain, with successive chains often involved to form "sheets".
... ... *protein denaturation: Usually irreversible complete
protein unfolding (without rupture of peptide bonds) and loss of
catalytic activity if the protein is an enzyme.
-------------------
SW 1999 6 Aug
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4. ON CATALASES IN BIOLOGICAL SYSTEMS
S.G. Kalko et al (University of Barcelona, ES) discuss catalases.
The need for protection against reactive oxygen species such as
hydrogen peroxide has led aerobic organisms to the development of
various enzymatic systems for the degradation of these compounds.
Among them, catalases are one of the most powerful mechanisms for
the protection against hydrogen peroxide. This family of enzymes
catalyzes the dismutation of hydrogen peroxide into water and
oxygen. The importance of catalases is clearly established by the
existence of a series of pathologies related to their
malfunctioning, e.g., increased susceptibility to thermal injury,
high rates of mutation, inflammation, and accelerated aging, and
the apparent importance of catalases explains their widespread
presence in living organisms. Three types of catalases have been
described in prokaryotes (cells without a nucleus): a) manganese-
based; b) catalase peroxidase; c) heme catalase. Only heme
catalases have been described for higher organisms, with the
mechanism of action of heme catalases complex and not fully
understood. Many structures of catalases have been described in
their native forms. These include 3 prokaryote enzymes from
Micrococcus luteus, Proteus mirabilis, and Escherichia coli, and
4 eukaryote enzymes from Penicillium vitale, a bovine catalase, a
catalase from yeast (S. cerevisiae), and human catalase. Besides
the large amount of experimental information on catalases,
including high-resolution structures, there are many unsolved
fundamental issues concerning these enzymes, including the
question of why these enzymes are so large and what are the
functions of various domains?
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JACS 2001 123: 9665
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5. ON THE CODING CAPACITY OF THE HUMAN GENOME
R.L. Strausberg and G.J. Riggins (National Cancer Institute, US)
discuss the human "transcriptome", the repertoire of actual
transcripts from the human genome. The potential coding capacity
of the human genome is currently a topic of great interest. The
number of genes predicted from the recent human-genome analysis
was at the lower end of previous estimates, which had ranged from
approximately 30,000 to 120,000. Whereas estimates of gene number
are likely to increase based on additional experimental evidence
and improved gene-finding algorithms, it is clear that gene
number is only one mechanism for creating the genetic diversity
required to encode the full complement of human proteins. The
scientific literature richly describes the presence and
functional significance of alternatively processed forms of human
transcripts that are derived from different transcription
initiation sites, alternative exon splicing, and multiple
polyadenylation sites. Determining the various transcript forms
and investigating the purpose of these complex mixtures of
instructions will be the next great endeavor toward understanding
human biology. Imperative to an elucidation of the transcriptome
will be the development of new technologies and scientific
strategies. We will need to identify and analyze not only
different transcripts from a single gene, but we will also need
to examine the entirety of the transcript population of cells and
tissues so that we can begin to understand the networks of
interactions encoded by various transcript forms. Undoubtedly,
innovation will be a hallmark of transcriptome research for the
next several years.
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PNAS 2001 98:11837
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6. ADAPTATION AND NEURAL CODES
A.L. Fairhall et al (NEC Research Institute, US) discuss adaptive
neural codes. In 1954, it was suggested by F. Attneave that
neural codes may constitute efficient representations of the
sensory world. Within the framework of information theory,
efficient coding requires a matching of the coding strategy to
the statistics of the input signals. Recent work demonstrates
that the sequences of action potentials from single neurons
provide an efficient representation of complex dynamic inputs,
that adaptation to the distribution of inputs can occur in real
time, and that the form of the adaptation can serve to maximize
information transmission. However, adaptation involves
compromises. An adaptive code is inherently ambiguous: the
meaning of a spike or a pattern of spikes depends on context, and
resolution of this ambiguity requires that the system
additionally encode information about the context itself. In a
dynamic environment, the context changes in time and there is a
trade-off between tracking rapid changes and optimizing the code
for the current context. The authors report they examined the
dynamics of adaptation to statistics in motion-sensitive cells in
the visual system of a fly (Calliphora vicina), and they find
that different aspects of adaptation occur on timescales that
range from tens of milliseconds to several minutes. The speed of
adaptation to a new input distribution must be limited by the
need to collect statistics. Adaptation of the neural input/output
relation to optimize information transmission approaches this
theoretical maximum speed. This rapid adaptation of the
input/output relation leaves the longer timescales in the
response dynamics as a nearly independent channel for
information, resolving potential ambiguities of an adaptive code.
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NAT 2001 412:787
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7. 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.
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PNAS 2001 98:11849
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SCIENCE-WEEK 16 Nov 2001 http://scienceweek.com
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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.
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NAT 2001 412:397
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PRAXIS 10 Sep 2001 http://scienceweek.com/praxis
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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."
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CEN 8 Jun 98
SW 19 Jun 98
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8. ON CATION-PI ELECTRON INTERACTIONS IN PROTEINS
A. Gapeev and R.C. Dunbar (Case Western Reserve University, US)
discuss cation-pi interactions. There is much debate concerning
the importance of cation-pi interactions in protein structure and
energetics. In situations where a metal ion performs a structural
role, or (more commonly) binds to an accessible surface site on a
protein, there is the possibility that the metal-ion binding
involves cation interaction with an aromatic side chain. Gas-
phase ion chemistry can substantiate such possibilities with
accurate measurements of the gas-phase binding affinities of
aromatic sites. Protein binding will typically involve extensive
intramolecular metal-ion chelation, so that particularly relevant
model sites are those, like the amino acids themselves, involving
extensive chelation. A recent study [V. Rhyzov et al (2000)] of
the alkali-cation affinities of the aromatic acids phenylalanine,
tyrosine, and tryptophan addressed these questions both
experimentally and computationally, but this study produced a
surprisingly large discrepancy between experimental and computed
cation binding energies for these systems. For example, for
sodium ion-phenylalanine, the computed binding affinity was 6.5
kilocalories per mole larger than the experimental result.
Another reflection of the same problem appeared in the
experimental comparison of binding to alanine and to the aromatic
amino acids. In general, computational predictions produce larger
cation-pi contributions than experimental measurements, and the
importance of such contributions in highly chelated and strained
systems such as proteins remains unresolved.
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JACS 2001 123: 8360
J. Amer. Soc. Mass Spectrom. 2000 11:1037
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9. COMPARATIVE GEOLOGY OF EARTH AND MARS
Maria T. Zuber (Massachusetts Institute of Technology, US)
discusses the geology of Mars. The difference in the geological
evolution of Mars compared to Earth is due primarily to the
smaller size of Mars. The radius of Mars is approximately half
that of the Earth, and so Mars probably heated up and cooled off
more quickly. As a consequence, geological activity manifest as
*tectonism, volcanism, and the associated release of volatiles
should have occurred relatively earlier for Mars than for Earth.
On Earth, convective cooling of the interior drives the motions
of surface plates (*tectonic plates) and is accompanied by the
creation of seafloor at mid-ocean ridges and the consumption of
plates at *subduction zones. In contrast, Mars is currently a
single-plate planet with a thick and rigid outer shell. But it is
possible that earlier in Martian history, when internal heat loss
was more intense, the planet displayed thinner and possibly even
mobile plates. Understanding the evolution of the crust and
mantle of Mars has been aided significantly by orbital global
geophysical measurements of topography, gravity, and magnetics,
Earth-based and orbital spectra, orbital- and lander-scale images
of the surface, and geochemical measurements of Martian
meteorites. These data collectively tell the story of an early
and dynamic Martian interior. The surface of Mars is now composed
of a mixture of relatively pristine *igneous rocks overlain by
highly oxidized weathering products that constitute the
relatively bright dust and soils. The reddish color of the
Martian surface is due to the presence of ferric iron-bearing
minerals in the oxidized surface layer.
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NAT 2001 412:220
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Notes:
... ... *tectonism: In general, deformation with the crust and
its consequent structural effects.
... ... *tectonic plates: The term "lithosphere" refers to the
outer layer of the Earth, comprising the crust and upper mantle,
and extending to a depth of 50 to 70 kilometers. The traditional
view of tectonics (changes in the structure of the Earth's crust)
is that the lithosphere consists of a strong brittle layer
overlying a weak ductile layer. "Plate tectonics" is the current
consensus theory that the Earth's lithosphere is broken into
fairly rigid plates, seven or eight major plates and many smaller
plates, and that convection within the underlying less rigid
"asthenosphere" causes the plates (and the associated continents
and crust) to move relative to each other.
... ... *subduction: The term "subduction" refers to the
process of underthrusting of the edge of an oceanic plate (see
following notes) into the mantle underlying an adjacent plate.
... ... *igneous rocks: Igneous rocks are rocks that have
congealed from a molten mass.
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Related Background:
PLANETARY SCIENCE: ON THE SEDIMENTARY ROCKS OF EARLY MARS
The term "early Mars" refers to the first 600 to 1000
million years after the planet first formed, and corresponds to
the time of intense impact cratering in the Solar System and the
emergence of life on Earth. Martian geochronology is divided into
3 periods: the Noachian period, the earliest, is defined as the
period dominated by heavy impact cratering and widespread
degradation of the cratered terrains; the Hesperian period,
generally thought to be a short transitional time as the impact
rate and other geomorphic processes tapered off and major ridged
plains formed to cover considerable tracts of cratered terrain;
and the Amazonian period, the recent period that includes Mars as
it is seen today. The absolute ages of these periods are not
known, but attempts have been made to estimate the ages by
assuming that the Martian cratering rate is some function of the
lunar cratering rate. In the present context, the Noachian period
is taken as the period prior to 3.5 billion years ago, and the
Amazonian period is taken to be the period up to the present from
the time-frame of approximately 3.5 to 1.8 billion years ago.
The Mars Global Surveyor spacecraft was launched in November
1996 and achieved orbit about Mars in September 1997. The
spacecraft carries the Mars Orbiter Camera, which consists of
three cameras: a narrow-angle system that obtains high spatial
resolution images (1.5 to 12 meters per pixel), and red and blue
wide-angle cameras to acquire regional and global views (0.24 to
7.5 kilometers per pixel).
The term "subaerial processes" refers to processes "under
the atmosphere"; the term "eolian (aeolian) processes" refers to
processes involving wind; the term "lacustrine" refers to lakes.
... ... M.C. Malin and K.S. Edgett (Malin Space Science Systems,
US) present an analysis of apparent sedimentary rocks of early
Mars, the analysis based on photographs obtained by the Mars
Orbiter Camera. The authors make the following points:
1) The authors point out that one of the primary questions
concerning the Noachian period is whether it was warmer and
wetter than the cold and arid Mars we see today, such that liquid
water could persist on the surface of Mars for thousands to
millions of years. Similarly, a key question regarding the
Amazonian period is whether there were climate excursions after
the present cold and dry conditions were established, climate
excursions that again allowed liquid water to persist on the
surface long enough for lakes or seas to have occupied certain
geological chasms and many impact craters around the surface of
the planet. Speculative affirmative answers to both of these
questions are widely cited to support the idea that Mars may have
had conditions favorable to the development and persistence of
life.
2) The authors present geologic evidence that the above two
hypotheses are linked, that the materials in craters in chasms
considered for 20 years to be Amazonian in age were instead
formed in the Noachian period, that there are many more outcrops
of these materials than previously known, that they could indeed
represent sediment deposited in lakes, and that they are a small
part of a substantially more complex and previously unanticipated
Martian history.
3) Specifically, the authors present evidence that layered
and massive outcrops on Mars, some as thick as 4 kilometers,
display the geomorphic attributes and stratigraphic relations of
sedimentary rock. Repeated beds in some locations imply a dynamic
depositional environment during early Martian history. Subaerial
(e.g., eolian, impact, and volcaniclastic) and subaqueous
processes may have contributed to the formation of the layers.
The apparent affinity of these layers for impact craters suggests
dominance of lacustrine deposition; alternatively, the materials
may have been deposited in a dry subaerial setting in which
atmospheric density and variations of atmospheric density
mimicked a subaqueous depositional environment. The source
regions and transport paths for the material have apparently not
been preserved.
4) The authors conclude: "When applied to the two questions
posed at the outset of this research article, our results show no
evidence for climate excursions in the Amazonian but do provide
evidence that can be used to support the contention that Mars in
the Noachian was warm enough to be wet enough to sustain bodies
of liquid water on its surface. But [our results] can also be
used to argue that Mars was very different from any of our
previous views."
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SCE 2000 290:1927
SW 2000 22 Dec
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10. ON THE COMPOSITION OF THE MOON
Paul D. Spudis (Lunar and Planetary Institute, US) discusses
recent data concerning the composition of the Moon. In 1994, the
Clementine mission mapped the global topography and color of the
Moon, and in 1998, the Lunar Prospector spacecraft mapped the
Moon's chemistry and gravity from a lower orbit. Before these two
orbital missions, knowledge about lunar surface chemistry was
largely based on samples brought back by the Apollo and Luna
missions. These samples showed that the highlands of the Moon are
rich in aluminum and poor in iron and magnesium. The new data
confirm this picture on a global scale, with some subtle but
important variations. Huge regions of the highlands are extremely
low in iron, and these regions are believed to be composed of an
aluminum-rich rock type called anorthosite, the only low-iron
rock type found on the Moon. Anorthosite forms when molten rock
crystallizes slowly, allowing low-density and aluminum-rich
minerals to float to the top of the magma body. The abundance of
anorthosite in the highland crust strongly supports the notion
that the outermost layer of the Moon was once nearly completely
molten, forming a "magma ocean". The isotopic composition of
lunar anorthosite samples indicates that the magma ocean must
have occurred early in the evolution of the Moon, while the
Clementine data show that it was a global event. The only known
source of sufficient heat for such an event is very rapid
accretion, as expected if the Moon formed as a result of a giant
impact between Earth and a massive asteroid.
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SCI 2001 293:1779
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11. HYDROGEN MARKERS IN ASTROPHYSICS
Robert Braun (Netherlands Foundation for Research in Astronomy,
NL) discusses the use of hydrogen emissions in astrophysics.
Hydrogen is the most abundant element in the Universe, accounting
for approximately 70 percent of the total mass in baryons
(particles such as protons and neutrons that experience the
strong nuclear force). In addition to being ubiquitous, the
hydrogen atom acts as an electric and magnetic dipole, giving
rise to radiation interactions that have enormous diagnostic
value in observational astronomy. The electric dipole of hydrogen
has long been exploited in astronomy, and since the recombination
spectrum of hydrogen was first calculated approximately 100 years
ago by J.J. Balmer and T. Lyman, this radiation has been used to
study emissions from energized regions and absorption by
quiescent regions at ever greater distances. The emission line
strength is directly proportional to the number of ionizing
photons, so strongly irradiated regions, such as the central
regions of quasars, can be detected even at extremely large
distances. The current record-holder is at a redshift of 6.28:
light reaching us from this distance has traveled for
approximately 95 percent of the age of the Universe. In contrast
to its electric dipole properties, the magnetic dipole properties
of hydrogen give rise to a much more subtle interaction: the tiny
energy difference between parallel and anti-parallel spins of the
proton-electron system of atomic hydrogen corresponds to a radio
photon with a wavelength at rest of 21.12 centimeters, and in
1945 Henk van de Hulst (1918-2000) predicted that this transition
might lead to an observable phenomenon. In 1951, the emission
from atomic hydrogen clouds was detected in our own Galaxy, and
now M.A. Zwaan (2001) report the first detection of the hydrogen
21 centimeter emission in another galaxy comparable to our own.
-----------
SCI 2001 293:1781,1800
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SCIENCE-WEEK 16 Nov 2001 http://scienceweek.com
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12. ON THE CHEMISTRY AND BIOLOGY OF STRYCHNINE
M.J. Eichberg et al (University of California Berkeley, US)
discuss strychnine. An infamous poisonous alkaloid, strychnine
has been known to man for thousands of years, and to Western
medicine since the 16th century. Although in the past strychnine
has found applications as a mild stimulatory tonic and appetite
enhancer, the most common uses today are as a rodenticide and
animal stimulant. Isolated in quantity from the Southeast Asian
tree Strychnos nux-vomica and the plant Strychnos ignatii, in
which the alkaloid is present in concentrations as high as 1.5 to
2 percent, strychnine toxicity arises from the blocking of
postsynaptic inhibition in the spinal cord and lower brain stem
where it acts as a competitive ligand at the neuronal receptor
for glycine, an inhibitory neurotransmitter. As a high affinity
and highly selective antagonist, the alkaloid has been useful as
a tool in the structural characterization of this receptor, as
well as in numerous biochemical studies of the nervous system.
For an adult human, a lethal dose of strychnine is in the range
of 100 to 300 milligrams. Death is caused by asphyxiation, a
result of the intense convulsions induced by acoustic, tactile,
or visual stimuli and the subsequent respiratory paralysis.
Strychnine holds a special place in the history of organic
chemistry. First isolated in 1818, it was one of the first
alkaloids to be obtained in pure form. The pursuit of its
molecular structure presented a formidable challenge for
classical degradative strategies and lasted more than 60 years,
resulting in the publication of hundreds of papers. In 1946, R.J.
Robinson proposed the correct structure for strychnine. This
signaled the end of the era of classical structure elucidation,
and in 1950 final confirmation of the structure was obtained by
x-ray crystallography.
-----------
JACS 2001 123:9324
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SCIENCE-WEEK 16 Nov 2001 http://scienceweek.com
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13. IN FOCUS:
ON THE TREATMENT OF THE MENTALLY ILL IN 18TH CENTURY AMERICA
[Editor's note: Many have proposed that to know where we are and
where we might be going it is essential to know where we have
come from. The treatment of the mentally ill in industrialized
countries has changed so radically in the past few centuries
that a consideration of history often produces shock at the way
things were. Certainly, the way things were was not so good. And
also certainly, it can be argued that the changes that have
occurred have been due more to science and scientific education
of the public than to any independent evolution of public
sensibilities. The recognition of the brain not only as the
organ of mind, but also as an organ like other organs, an organ
susceptible to disease, disorder, poisoning, and biochemical
dysfunction, has perhaps been the most important contribution of
neuroscience to the public good. In any case, here is a piece of
history concerning early days in America.]
-----------------------
"Society needed to be protected from the insane, and it was this
second function -- hospital as jail -- that had taken precedence
when the [Pennsylvania] hospital opened in 1756. In those early
years, the lunatics were kept in gloomy, foul-smelling cells and
were ruled over by 'keepers' who used their whips freely. Unruly
patients, when not being beaten, were regularly 'chained to rings
of iron, let into the floor or wall of the cell... restrained in
hand-cuffs or ankle-irons,' and bundled into Madd-shirts that
'left the patient an impotent bundle of wrath.' A visiting
reverend, Manasseh Cutler, described the sorry scene: 'We next
took a view of the Maniacs. Their cells are in the lower story,
which is partly underground. These cells are about ten feet
square, made as strong as a prison... Here were both men and
women, between twenty and thirty in number. Some of them have
beds; most of them clean straw. Some of them were extremely
fierce and raving, nearly or quite naked; some singing and
dancing; some in despair; some were dumb and would not open their
mouths.' The lunatics also had to suffer the indignity of serving
as a public spectacle. After the hospital opened, visiting the
mad had quickly become a popular Sunday outing, similar to
visiting a zoo. Philadelphians were eager to get a glimpse of
these wretched creatures, with good sport on occasion to be had
by taunting them, particularly those restrained in irons and
easily roused into a rage. So frequent were the public's visits,
and so disturbing to the insane, that the hospital managers
erected a fence in 1760 'to prevent the Disturbance which is
given to the Lunatics confin'd in the Cells by the Great Numbers
of People who frequently resort and converse with them.' But even
an iron fence couldn't keep the public at bay, and so in 1762,
the hospital, trying to make the best of an unfortunate
situation, began charging a visitor's fee of four pence."
-----------
Robert Whitaker: _Mad in America_
(Perseus Publishing, Cambridge, MA 2002, p.4)
To be published February 2002.
http://www.amazon.com/exec/obidos/ASIN/0738203858/scienceweek
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SCIENCE-WEEK 16 Nov 2001 http://scienceweek.com
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14. FROM PRAXIS:
RELATION BETWEEN DEPRESSION AND OTHER MEDICAL ILLNESSES
S.P. Roose et al (Columbia University, US) discuss depression in
the context of other illnesses. Depression occurring in the
setting of a non-psychiatric medical illness is often considered
to be a psychological reaction: clinicians attribute the
patient's feelings of vulnerability, fear, and diminished self-
esteem to the onset of a severe illness. However, recent data
have forced reconsideration of this belief, and new models of the
relationship between depression and other medical illnesses have
emerged. Compelling evidence suggests that depression is an
independent risk factor that contributes to the development of
ischemic heart disease and increases cardiac mortality. However,
abandoning the concept of depression as a reaction to illness
seems premature, since the relationship between depression and
other illnesses is complex and may vary. Current and future
investigations will demonstrate whether treatment of depression
modifies lifetime cardiac risk and/or reduces mortality in
patients after myocardial infarction. In stroke, new
interventions may alter residual structural damage from ischemia
and may lower the incidence of post-stroke depression. The
relationship between treated erectile dysfunction and depression
supports the construct of reactive depression. In general,
depression coexisting with other medical illnesses may impair
recovery and rehabilitation, as well as produce increased risk of
morbidity and mortality. The authors suggest that recognition and
appropriate treatment of depression when it occurs concurrently
with severe or chronic illness remain essential for optimal
patient outcomes.
-----------
JAMA 2001 286:1687
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PRAXIS 19 Nov 2001 http://scienceweek.com/praxis
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SCIENCE-WEEK 16 Nov 2001 http://scienceweek.com
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15. SOURCES:
------------
AS: American Scientist; CEN: Chemical & Engineering News;
CR: Chemical Reviews; GD: Genes & Development;
GR: Genome Research; JACS: J. Amer. Chemical Society;
JAMA: J. Amer. Medical Association; JCE: J. Chem. Education;
MMWR: CDC Morbidity and Mortality Weekly Report; NAT: Nature;
NATM: Nature Medicine; NEJM: New England J. Medicine;
NS: New Scientist; NYT: New York Times; NYR: New York Review;
PNAS: Proceedings of the National Academy of Sciences;
PRL: Physical Review Letters; PT: Physics Today; PRAX: PRAXIS;
SA: Scientific American; SCI: Science; SW: ScienceWeek;
TS: The Scientist.
In the text, the affiliation following the names of authors is
the affiliation of the lead author.
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