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.

October 5, 2001 -- Vol. 5 Number 40

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The world's a bubble.
-- Francis Bacon (1561-1626)

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Section 1
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Contents of this Issue (Full reports in Section 2):

1. On Intermediate Filaments
2. Mechanical Behavior in Living Cells
3. On Apoptosis
4. Neurobiology: Potassium Inactivation
5. Origin of Biological Nitrogen Fixation
6. Molecular Evolution of Proteins
7. History of Science: Lazzaro Spallanzani
8. Small-Molecule Binding to RNA
9. Stabilization of Protein Helices
10. Leaf Sensors for Paleoclimate Carbon Dioxide
11. Hydrophobic Molecular Interactions
12. On Flavor-Switching of Solar Neutrinos
13. In Focus: On Statistical Regression
14. SW Archive: Popular Culture and Rational Inquiry
15. Sources

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Section 2
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1. ON INTERMEDIATE FILAMENTS
     The advent of electron microscopy in the 1950s, with
practical resolutions at that time of the order of 10 or 20
angstroms, completely changed our view of the interior of
biological cells, and for the first time networks of
interconnected filaments in protoplasm were recognized as a
cytoplasmic framework inside all cells. This framework, called
the "cytoskeleton", was demonstrated to be involved in at least
two basic functions: a) the provision of a scaffolding supporting
and organizing the cell interior, the scaffolding a structured
framework that permits cells to assume elaborate shapes, and
which organizes and guides interactions among intracellular
organelles; and b) The generation of movement, the cytoskeleton
containing elements that permit both movement of the cell as a
whole and movement of various intracellular components.
     The intracellular cytoskeleton is apparently constructed
from 3 classes of protein filaments: actin filaments
(microfilaments), microtubules, and intermediate filaments. In
some cases, a single type of filament is responsible for a
particular function; in other cases, interactions between
different filament types are involved.
... ... Robert D. Goldman (Northwestern University, US) discusses
the functions of intermediate filaments. These structures
represent one of the three major cytoskeletal systems found in
animal cells, their name derived from their 10-nanometer
diameter, which lies between that of smaller actin-containing
microfilaments and larger microtubules. The name, however, belies
their importance as critical players in the organization of cells
and tissues of vertebrate systems. Concerning function, it has
become apparent from studies of numerous human disorders, such as
those that cause blistering diseases of the skin, that
intermediate filaments play important roles in establishing and
maintaining the mechanical integrity of cells. Depending on the
cell type, intermediate filament proteins comprise anywhere from
1 to 85 percent of total cell protein, but despite these
quantities, intermediate filaments remain the least studied and
least understood of all cytoskeletal systems. Historically, there
are many reasons for this lack of understanding of their
structure and function, the most obvious reason relating to the
fact that the structural proteins that assemble into intermediate
filaments are not highly conserved. For example, humans contain
intermediate filaments that are encoded by over 50 different
members of a multi-gene family, with this family subdivided into
6 types on the basis of similarities in their amino acid
sequences. This is in stark contrast to the other cytoskeletal
components, whose core structures are comprised primarily of the
highly conserved subunits of microtubules, alpha- and beta-
tubulin, and actin, the major subunit of microfilaments.
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PNAS 2001 98:7659
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2. MECHANICAL BEHAVIOR IN LIVING CELLS
N. Wang et al (Harvard University, US) discuss mechanical
behavior in living cells. Mechanical stress-induced alterations
in cell shape are critical for control of many cell functions,
including growth, motility, contraction, and mechanotransduction.
These functional alterations are mediated through changes in the
internal cytoskeleton, which is composed of an interconnected
network of microfilaments, microtubules, and intermediate
filaments, the network linking the nucleus to surface adhesion
receptors. Advances in cell biology have resulted in better
understanding of the polymerization behavior and physical
properties of individual cytoskeleton filaments as well as of
gels composed of combinations of filaments. However, the material
properties measured in vitro neither explain nor predict complex
mechanical behaviors that are observed in living cells. At the
same time, engineers have approached the problem of how cells
stabilize their shape by developing mechanical models without
considering molecular specificity. For example, the living cell
is often modeled as a continuum that contains an elastic cortex
surrounding a viscous or viscoelastic fluid. A more complex
variation includes an elastic nucleus within a viscous cytoplasm.
These models provide reasonable empirical fits to measure elastic
moduli and viscosity in cells under specific experimental
conditions, but they cannot predict from mechanistic principles
how these properties alter under different challenges to the
cell. Continuum models also assume that the load-bearing elements
are infinitesimally small relative to the size of the cell, and
thus they do not provide insight into how distinct molecular
structures, such as cytoskeleton filaments, contribute to cell
mechanics. This is a critical limitation, since it is not
possible to explain how mechanical forces regulate cell function
without linking mechanics to microstructure and molecular
biochemistry.
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PNAS 2001 98:7765
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3. ON APOPTOSIS
Gerry Melino (University Tor Vergata, IT) discusses apoptosis.
Individual biological cells in multicellular organisms face three
choices: to divide (mitosis), to specialize (differentiation), or
to commit suicide (apoptosis), and the balance between these
choices ensures tight regulation of cell numbers within
organisms. As a consequence of continuing ordinary mitosis
without cell death, for example, an 80-year-old person would have
2 tons of bone marrow and lymph nodes and an intestinal tract 16
kilometers long. Since apoptosis is more than 20 times faster
than mitosis, sightings of cells dying from apoptosis are rare.
In contrast to passive cell death (necrosis), which is
characterized by leakage and inflammation, apoptotic cells are
engulfed and degraded by neighboring cells without a trace.
Various morphologies currently regarded as apoptotic have been
observed since the 19th century, but it was not until the 1980s
that apoptosis was recognized as a specific process when R.
Horvitz et al mapped the fate of every cell in the nematode worm
C. elegans, including those cells committed to die. It emerged
that programmed cell death is determined by a handful of genes,
and that these "master switches" have been conserved in evolution
so that they, or rather their equivalent gene families, still
orchestrate apoptosis in mammals. The idea has gradually emerged
that the stability of the body is maintained by signals that
control life and death of single cells. This is a powerful
concept, implying that there are specific survival and death
signals, and corresponding receptors on cell surfaces. Such
social control of life and death are vital in complex
multicellular networks such as the immune system and the nervous
system, where communication between cells is crucial.
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NAT 2001 412: 23
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Related Background:
CELL BIOLOGY: APOPTOSIS AND CASPASES
     From one perspective, the adult human organism is a highly
integrated colony of approximately 10^(12) individual biological
cells of various types, and for the sake of the viability of the
entire organism, many of these cells, particularly cells which
for one reason or another are defective, must be continually
eliminated and replaced. Programmed elimination of cells also
occurs during embryonic and childhood development, when
specialized tissues form and many normal cells must be discarded
as part of this formation.
     In general, the term "apoptosis" refers to programmed cell
death, whether as a part of normal tissue differentiation and
development, or as a program activated in a defective cell. In
the molecular biology of cancer, for example, apoptosis involves
programmed cell death provoked by proteins expressed by so-called
"tumor suppressor genes": malignant cells are essentially
defective cells with a deactivated apoptosis program, and this
deactivation of apoptosis allows malignant cells to survive and
replicate.
     Proteases are a class of enzymes that hydrolyze proteins,
splitting them into various groups of subunits, with the sites of
hydrolysis dependent on the particular enzyme and the protein
substrate, and a caspase is a type of protease implicated in
apoptosis.
     The term "endoplasmic reticulum" refers to a complex system
of flattened sacs in all biological cells that have a nucleus
(eukaryotes). The endoplasmic reticulum is the site of many
important syntheses, including the production of new surface
membrane and the intracellular transport of various biochemical
entities.
... ... Huseyin Mehmet (Imperial College, UK) presents a
commentary on current research concerning apoptosis and caspases,
the author making the following points:
     1) In the normal workings of the cell, apoptosis needs to be
tightly regulated by cellular mechanisms in order to avoid
unnecessary cell death and serious pathology (such as possibly
certain neurodegenerative diseases). One way in which the
prevention of unnecessary cell death is accomplished by the cell
is the physical separation of the various components of the
apoptotic machinery, so that only when the "death switch" is
actually tripped are the components involved in apoptosis brought
together and the suicide program activated. The two main cell
compartments now known to be involved in apoptosis are the plasma
membrane, where both death and survival receptors are located,
and the *mitochondria of cells, where several proteins that
regulate apoptosis reside.
     2) Among the most prominent apoptosis-specific enzymes are
the caspases, a family of cysteine-dependent aspartate-specific
proteases. These enzymes can be broadly divided into two groups:
a) initiator caspases (e.g., caspase-8 and caspase-9) whose main
function is activate other caspases; and b) executor caspases
(e.g., caspase-3, -6, and -7), which are responsible for
dismantling cellular proteins. The two main apoptotic pathways --
the death receptor pathway and the mitochondrial pathway -- are
activated by caspase-8 and caspase-9, respectively, both of which
are found in the cytoplasm. Caspase-8 is recruited by an
apoptosis-inducing signaling complex only when death receptors
are oligomerized after binding of specific ligands. In contrast,
caspase-9 is activated when *cytochrome-c is released into the
cytoplasm from the space between the inner and outer
mitochondrial membranes.
     3) T. Nakagawa et al (Nature 403:99 2000) have now
demonstrated that another caspase involved in apoptosis,
caspase-12, is localized in the endoplasmic reticulum. Caspase-12
is apparently specifically involved in apoptosis that results
from various biochemical stresses to the endoplasmic reticulum,
such as disruption of endoplasmic reticulum calcium ion
distributions. Apoptosis triggered through pathways that do not
involve the endoplasmic reticulum apparently does not result in
the activation of caspase-12.
     4) The author concludes that since caspases are central to
both normal programmed cell death and injury-dependent apoptosis,
any therapy that manipulates caspase activity must take into
account the possible effects on tissue viability. "If activation
of caspase-12 does turn out to be confined to only a narrow band
of cellular stress signals, it will be a promising potential
target for treating neurodegenerative diseases and cancer with
few side effects."
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NAT 2000 403:29
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Notes:
... ... *mitochondria: Organelles of the cell cytoplasm,
mitochondria are the principal energy source of the cell,
containing various enzymes involved in electron transport and
metabolic cycles.
... ... *cytochrome-c: The cytochromes are a system of electron-
transfer proteins with iron- or copper-porphyrin as a prosthetic
group. They are found in both animal and plant cells.
Cytochrome-c is found in mitochondria.
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SW 2000 21 Apr
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Related Background:
MOLECULAR BIOLOGY: APOPTOSIS, MITOCHONDRIA, AND CASPASES
Apoptosis (programmed cell death) is a rapid and specific process
involving the production of a number of enzymes in the cell
programmed to be destroyed. This programmed destruction is not
always harmful, or always the result of cellular damage of one
sort or another. In humans, for example, the lack of webbing
between fingers and toes is a result of apoptosis of cells of
webbing tissue occurring during embryological development, the
apoptosis in this case being a normal part of the larger
embryological program. In the mature organism, apoptosis is the
usual method of removing damaged cells after these cells are
recognized to be damaged by one mechanism or another. It is known
that normal cells carry an apoptosis receptor on their surfaces,
called CD95, and that when this surface receptor is cross-linked
by its specific ligand, this triggers the sequence of events
known as apoptosis. In the apoptosis sequence, certain
*proteolytic enzymes inside the cell are activated, and in
addition a variety of lipids that cause cell dysfunction are
synthesized. ... ... D.R. Green and J.C. Reed review the
involvement of *mitochondria with apoptosis in *metazoan cells,
and the authors make the following points: 1) The current
consensus among biologists is that approximately 2 billion years
ago the cells destined to become the ancestors of all *eukaryotes
entered into a partnership with an ancestor of today's *purple
bacteria, an ancestor that subsequently became the mitochondria
of today. 2) It has been hypothesized by several investigators
that the *endosymbiotic origins of mitochondria and the evolution
of aerobic metabolism in eukaryotes formed the basis for the
evolution of active cell death, which in metazoans is manifested
predominantly as apoptosis. Central roles for mitochondria as the
orchestrators  of apoptosis have been firmly established in many
systems. 3) In recent years it has become apparent that the
effectors of apoptosis are a family of intracellular proteases
known as caspases, although inhibiting these enzymes does not
always prevent apoptosis. 4) At least 3 general mechanisms have
been proposed for the involvement of mitochondria in the control
of cell life and death: a) disruption of *electron transport,
*oxidative phosphorylation, and adenosine triphosphate (ATP)
production; b) release of proteins that trigger activation of the
caspases family of proteases; c) alteration of cellular *redox
potentials. 5) In many apoptosis scenarios, the mitochondrial
inner electrical transmembrane potential collapses, indicating
the opening of large conductance channels through the inner
membrane. In contrast, certain stimuli can induce rupture of the
outer membrane of mitochondria and release of caspase-activation
proteins. The authors conclude: "Perhaps a few hundred million
years ago, either convergent or divergent evolutionary processes
allowed the ... fundamental framework for bacterial warfare to be
incorporated into the cell death mechanisms used by animal cells,
thereby establishing mitochondria as important participants not
only in animal cell life but also in active cell death." ... ...
In a companion and contiguous review of caspases and apoptosis,
N.A. Thornberry and Y. Lazebnik point out the following: 1)
Proteolysis is irreversible, which implies that regulation of
proteases is limited to control of their activity and
availability of substrate -- the only known way of "correcting" a
cleaved protein is to make it afresh. 2) Most proteases are
synthesized as precursors that have little if any catalytic
activity. The precursor is usually converted to the active enzyme
by proteolytic processing mediated either by another protease or
by autocatalysis. Thus large amounts of precursor can be
accumulated in advance and activated on demand. 3) Proteases can
regulate their own activation, resulting in an exponential rate
of activation. 4) Where there are proteases there are inhibitors,
and these inhibitors regulate the concentration of active
protease in the cell. 5) Proteolytic reactions can be specific,
determined by a combination of primary, secondary, or tertiary
structures of protein substrates. Proteolysis that governs
critical biological processes such as the cell cycle or cell
death is highly specific and involves a restricted set of
substrates. 6) The various caspases share similarities in amino
acid sequence, structure, and substrate specificity. 7) Caspases
are among the most specific of proteases with an unusual and
absolute requirement for cleavage after aspartic acid and
recognition of at least 4 amino acids terminal to the cleavage
site. 8) The strict specificity of caspases is consistent with
the observation that apoptosis is not accompanied by
indiscriminate protein digestion, but rather a select set of
proteins is cleaved in a coordinated manner, usually at a single
site, resulting in a loss or change in function. 9) Apoptotic
events include DNA fragmentation, *chromatin condensation,
*membrane blebbing, cell shrinkage, and disassembly into
membrane-enclosed vesicles (apoptotic bodies). In vivo, this
process culminates with the engulfment of apoptotic bodies by
other cells, preventing complications that would result from a
release of intracellular contents. In apoptosis, these changes
occur in a predictable reproducible sequence and can be completed
with 30 to 60 minutes. The authors conclude: "Substantial
progress has been made in understanding the structural and
catalytic properties of active caspases and their contribution to
apoptosis. The goal for future research is to understand the
regulation of these enzymes. This should facilitate efforts to
rationally manipulate the apoptotic machinery for therapeutic
gain."
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SCI 1998 281:1309,1312
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Notes:
... ... *proteolytic enzymes: These enzymes, also called
"proteases", split proteins and thereby degrade them. The enzymes
catalyze the hydrolysis of peptide bonds, fragmenting proteins
into polypeptide chains, and fragmenting polypeptide chains into
constituent amino acids. Sometimes proteolytic enzymes and
proteases are distinguished, with the term "proteases" reserved
for proteolytic enzymes with high specificity for peptide bonds
between particular amino acids.
... ... *mitochondria: Mitochondria are double-membrane enclosed
organelles of cells that are involved with several important
biochemical pathways, including electron transport and oxidative
metabolism, and across the membrane of the mitochondrion there
exists a potential difference apparently due primarily to a
concentration gradient of hydrogen ions. Various types of
eukaryotic cells may contain from a few to several thousand
mitochondria in each cell type. The mitochondria are relatively
large cylindrical structures up to 10 microns long and up to 2
microns in diameter.
... ... *metazoan cells: Metazoans are multicellular animals.
... ... *eukaryotes: Cells (and organisms consisting of such
cells) that contain intracellular membrane-bound compartments
such as a nucleus (membrane-bound "organelles").
... ... *purple bacteria: Specifically, any of the various
photosynthetic bacteria that contain bacteriochlorophyll, and are
thus distinguished by purplish or reddish-brown pigments. But the
term "purple bacteria" is sometimes used as a synonym for the
phylum Proteobacteria, a general category comprising a large
number of diverse forms.
... ... *endosymbiotic: Endosymbiosis is an arrangement in which
one organism lives inside another organism, but the term is
usually restricted to arrangements of mutual benefit, thus not
including parasite-host relationships. A number of eukaryotic
cell organelles (including mitochondria) are believed to have
originated from endosymbiotic relationships between eukaryotic
cells and simpler cells.
... ... *electron transport: Refers to a sequence of steps in the
final stage of the aerobic respiration biochemical pathway in
which high energy electrons are effectively passed through a
series of membrane-bound carrier molecules to support a proton
gradient involved in energy storage. The term "transport" here
refers essentially to a chemical flow diagram and not necessarily
to an actual spatial translocation of electrons.
... ... *oxidative phosphorylation: Production of ATP during
aerobic respiration. It takes place in the mitochondria of
eukaryotic cells and requires molecular oxygen as a terminal
electron acceptor.
... ... *redox potentials: Chemical potentials in a chemical
reaction involving the simultaneous reduction and oxidation of
two compounds by a transfer of electrons between them.
... ... *chromatin: The entire complex of a eukaryotic
chromosome, including DNA, chromosomal proteins, and chromosomal
RNA.
... ... *membrane blebbing: Refers to the macroscopic blistering
of the surfaces of cells when they die under certain conditions.
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SW 1998 2 Oct
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4. NEUROBIOLOGY: POTASSIUM INACTIVATION
Richard W. Aldrich (Stanford University, US) discusses potassium
inactivation. The ion channels that span cell membranes and
moderate the transmembrane flow of electrical currents regulate a
whole range of biological phenomena. The channels themselves are
controlled in a variety of ways, one notable group being
"voltage-gated", i.e., they open in response to (and then cause)
changes in membrane potential difference [*Note #1]. In 1952,
A.L, Hodgkin and A.F. Huxley demonstrated the physiological
importance of the additional process of channel inactivation, but
pointed out that "details of the mechanism will probably not be
settled for some time." Inactivation has been extensively studied
in two of the main types of ion channel, those that allow the
passage of sodium or potassium ions. In sodium channels,
inactivation is important for the termination of the nerve
impulse and for setting the period before the nerve cell can fire
again. In potassium channels, inactivation shapes the electrical
signaling properties of many types of nerve, muscle, and other
cells. Since the work of Hodgkin and Huxley, the application of
increasingly sophisticated techniques has led to progressively
greater understanding of inactivation (which appears to occur in
similar ways in both types of channel). New findings of MacKinnon
et al (2001) suggest a detailed molecular view of channel
inactivation that fits well with the results of a variety of
techniques over the past half century.
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NAT 2001 411:643,657
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Notes:
... ... *Note #1: The opening of an ionic channel causes an
increases in permeability to that ion, which itself causes a
change in the potential difference across the membrane. In
general, the global potential difference is related to the
concentration gradient of a particular ion by a factor derived
from the permeability of that ion through the membrane.
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SCIENCE-WEEK 5 Oct 2001 http://scienceweek.com
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Related Background:
STRUCTURE OF THE VOLTAGE-GATED SODIUM CHANNEL
     Electrical signals in the nervous system are generated by
the movement of ions across the nerve cell membrane. These ionic
currents flow through aqueous pores of membrane proteins known as
"ion channels", and these channels vary in ion selectivity, with
some channels specifically permeable to sodium or potassium or
calcium ions.
     Certain sodium, potassium, and calcium channels are
"voltage-gated" -- their permeability is switched on and off by
changes in the potential difference across the cell membrane --
and these channels essentially control the dynamic electric
activity of nerve and muscle cells.
     The voltage-activated sodium channel from eel electric
organs (of relevance in this report) is a single molecule of
approximately 1800 amino acids, within which are 4 repeating
domains. These domains are architecturally equivalent to the
subunits of other ion channels. Within each domain, there are
apparently 6 membrane spanning regions connected by intracellular
and extracellular polypeptide loops. The eel channel is
apparently representative of a diverse family of channel proteins
present in nerve and muscle fibers.
     Fifty years ago, the existence of such specific protein
channels was not even conceived, although it was recognized there
had to be some explanation for specific ion currents in nerve and
muscle cells. Thirty years ago, the existence of such channels
was vaguely proposed, but with hardly any molecular information.
In the past decade, ion channels have become definitive
structural entities.
... ... C. Sato et al (7 authors at 5 installations, JP CH)
present a report on the structure of the sodium-sensitive ion
channel, the authors making the following points:
     1) The authors point out that the voltage-sensitive sodium,
potassium, and calcium channels operate together to amplify,
transmit, and generate electric pulses in animals. Sodium and
calcium channels are involved in cell excitation, neuronal
transmission, muscle contraction, and many functions that relate
directly to human diseases. Sodium channels, which are
glycosylated proteins with a relative molecular mass of
approximately 300,000, are responsible for signal transduction
and amplification, and are chief targets of anesthetic drugs and
neurotoxins.
     2) The authors report the 3-dimensional structure of the
voltage-sensitive sodium channel of the eel Electrophorus
electricus. The structure was determined at 19 angstroms
resolution by helium-cooled cryo-electron microscopy and single-
particle image analysis of the solubilized sodium channel. The
authors report the channel has a bell-shaped outer surface of 135
angstroms in height and 100 angstroms in side length at the
square-shaped bottom, and a spherical top with a diameter of 65
angstroms. Several inner cavities are connected to 4 small holes
and 8 orifices close to the extracellular and cytoplasmic
membrane surfaces. Homologous voltage-sensitive calcium and
tetrameric potassium channels, which regulate secretory processes
and the membrane potential, may possess related structure.
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NAT 2001 409:1047
SW 2001 23 Mar
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Related Background:
NEUROBIOLOGY: ATOMIC SCALE MOVEMENTS IN POTASSIUM CHANNELS
The functional electrical activity of nerve cells is based
essentially on the rapid movements of ions across the membranes
of these cells, especially the movements of sodium and potassium
ions. These ion movements occur through special pores ("ion
channels") in the cell membrane, and one of the important
problems during the past few decades has been to characterize
these ion channels at the molecular level. Most ion channels are
selective, allowing only ions of a certain type to pass, and an
individual cell has ion channels with various ion selectivities.
The selectivity of an ion channel can be "gated", the channel
effectively opened or closed, and ion channels are said to
"voltage-gated" or "ligand-gated", depending on how the change in
selectivity is provoked. The term "voltage-gated" refers to the
opening or closing of an ion channel by changes in the electrical
potential across the membrane, while the term "ligand-gated"
refers to opening and closing of an ion channel by interactions
between ligands and membrane receptors. It has become apparent
that voltage-gated ion channels are transmembrane proteins
consisting of 4 identical subunits, each of which contains 6
transmembrane segments. Studies of the potassium ion channel have
identified two segments that contain several charged protein
residues, and these charged residues apparently sense changes in
the potential difference across the membrane and form part of the
membrane "voltage sensor". Although these regions apparently
undergo conformational changes in response to changes in membrane
potential, little is known about the nature of these changes.
... ... A. Cha et al (4 authors at 2 installations, US) report a
study of molecular movements of the voltage-sensing region in a
potassium channel, the authors making the following points:
     1) The authors used *lanthanide-based fluorescence resonance
energy transfer to measure distances between *Shaker potassium-
channel protein subunits at specific residues. Voltage dependent
distance changes of up to 3.2 angstroms were measured at several
sites near one of the charged protein segments (S4). These
movements directly correlated with electrical measurements of the
voltage sensor, establishing a link between physical changes and
electrical charge movement.
     2) The authors suggest that the measured distance changes
indicate that the region associated with the S4 segment undergoes
a rotation and possible tilt, rather than a large transmembrane
movement, in response to voltage.
     3) The authors conclude: "These results demonstrate the
first in situ measurement of atomic scale movement in a
transmembrane protein."
... ... In a contiguous and related report, K.S. Glauner et al (4
authors at University of California Berkeley, US) present a study
of voltage-sensor movements of a potassium channel, the authors
making the following points:
     1) The authors used fluorescence resonance energy transfer
as a "spectroscopic ruler" to determine distances between S4
subunits in the Shaker potassium channel in different gating
states.
     2) The authors conclude their experimental evidence is
consistent with the S4 subunit being a tilted helix that twists
during activation. The authors propose that helical twist
contributes to the movement of charged side chains across the
membrane electric field and that this movement is involved in
coupling voltage-sensing to gating.
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NAT 1999 402:809,813
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Notes:
... ... *lanthanide-based fluorescence resonance energy transfer:
The term "fluorescence resonance energy transfer" (also called
"fluorescence energy transfer") refers to energy transfer between
two fluorophores (chemical groups or molecules capable of
fluorescence). If the two fluorophores are attached to a molecule
at different positions, observations of fluorescence energy
transfer between them can be used to determine the distance
between the two attachment positions. Lanthanide-based resonance
energy transfer is a modification of conventional fluorescence
resonance energy transfer in which a long-lived lanthanide donor
transfers energy in a distance-dependent manner to a conventional
organic fluorescent acceptor. This technique has previously been
used to measure angstrom-scale conformational changes in
proteins.
... ... *Shaker potassium-channel protein: The term "Shaker" here
refers to a mutant of the fruitfly Drosophila, the mutant
exhibiting intense shaking of the legs and body in response to
exposure to a volatile anaesthetic. Genetic analysis of the
mutation some years ago led to the sequencing of a Drosophila
gene expressing a potassium-channel protein, the shaking of the
insect apparently resulting from a mutation in this gene, with
the mutation producing long-lasting potassium ion currents when
nerve fibers are activated. Once the Shaker gene was sequenced, a
conventional procedure was developed in the 1980s to have this
gene expressed in frog egg cells (oocytes) in order to advance
the study of the behavior of potassium ion channels. Thus, the
potassium ion channels in this report are ion channels derived
from the fruitfly Drosophila and expressed in the frog Xenopus
laevis egg cell. The essential aspects of frog oocytes is that
they are large cells (up to 1 millimeter in diameter), and the
introduction of foreign *messenger RNA into the egg cell readily
results in the production of the protein encoded by the
introduced messenger RNA.
... ... *messenger RNA: (mRNA) The ribonucleic acid molecule
transcribed from DNA that carries the coded information
specifying the sequence of amino acids in a protein.
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SW 2000 11 Feb
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Related Background:
STRUCTURAL REARRANGEMENTS IN POTASSIUM CHANNEL GATING
Ion channels are protein channels in cell membranes that allow
ions to pass from extracellular solution to intracellular
solution and vice versa. Most ion channels are selective,
allowing only certain ions to pass, and an individual cell has
ion channels with various ion selectivities. The selectivity of
an ion channel can be "gated", the channel effectively opened or
closed, and ion channels are said to voltage-gated or ligand-
gated, depending on how the change in selectivity is provoked.
The opening of a previously closed ion channel produces a sudden
increase in transmembrane conductance for that ion, and the
process is called "activation". The gating of the movements of
ions through ion channels is of considerable importance for
various processes in all living systems, and forms the basis of
the electrical activity of all nervous systems. Recently (see
background material below), an important advance in ion-channel
research occurred with the experimental determination of the
crystal structure of a potassium channel (KcsA) in the bacterial
species Streptomyces lividans. The structure involves a
tetrameric complex with a centrally located pore framed by the
apposition of individual subunits, each subunit with 2
transmembrane helices (TM1 and TM2) flanking a "selectivity
filter". Intensive studies of this potassium channel in *planar
lipid bilayers have been in progress in a number of laboratories.
... ... E. Porozo et al (3 authors at University of Virginia, U)
now report a study of the structural rearrangements underlying
activation gating in this potassium channel, the study using
*spin-labeling methods and *electron paramagnetic resonance
spectroscopy. The authors report that a comparison of the closed
and open conformations of the channel revealed periodic changes
in spin-label mobility and intersubunit *spin-spin interaction
consistent with rigid-body movements of the two transmembrane
helices TM1 and TM2. These changes involve translations and
counterclockwise rotations of both helices relative to the center
of symmetry of the channel. The movement of TM2 apparently
increases the diameter of the permeation pathway along the point
of convergence of the four subunits, thus opening the pore.
Although the extracellular residues flanking the selectivity
filter remained immobile during gating, small movements were
detected at the *C-terminal end of the pore helix, and the
authors suggest this has possible implications for the gating
mechanism.
-----------
SCI 1999 285:73
-----------
Notes:
... ... *planar lipid bilayers: The cell membrane consists of a
lipid bilayer and associated proteins, the ensemble approximately
75 to 100 angstroms in thickness. Similar membranes are also
found within a cell surrounding various organelles. Lipid
bilayers are spontaneously forming self-organizing bimolecular
layers of certain molecules (lipids) with long nonpolar chains
terminated by a polar group. In addition to their presence in
cell membranes, such molecules (surfactants) are also found in
soaps. A variety of artificial lipid bilayer membrane systems can
be investigated in the laboratory.
... ... *spin-labeling methods: A "spin-label" is a synthetic
paramagnetic organic free radical incorporated in a macromolecule
or assemblage of macromolecules and used, in particular, in
electron paramagnetic resonance spectroscopy.
... ... *electron paramagnetic resonance spectroscopy: (ESR) This
technique is used to investigate paramagnetic centers in a
molecular system. Only electrons whose spin is not paired with
the oppositely directed spin of another electron give an ESR
signal. With this technique, information can be obtained about
certain transitional ions, free radicals, and free electron
centers. A probe giving an ESR signal can be incorporated into
membrane lipids or attached to proteins to enable otherwise
inaccessible systems to be studied. Through analysis of ESR
spectra, rates of molecular motion and relative orientation of
spin-labeled molecules whose motion is restrained by surrounding
molecules can be determined. Measurements of rates of molecular
motion and molecular orientation have proved to be important in
the study of a variety of biological problems.
... ... *spin-spin interaction: In this context, an interaction
of two neighboring paramagnetic entities, the interaction
producing a change in ESR signal.
... ... *C-terminal end: In general, this refers to the end of
any polypeptide chain at which the 1-carboxy function of a
constituent alpha-amino acid is not attached in peptide linkage
to another amino acid residue.
-----------
SW 1999 13 Aug
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SCIENCE-WEEK 5 Oct 2001 http://scienceweek.com
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Related Background:
ANALYSIS OF POTASSIUM ION MEMBRANE CHANNEL STRUCTURE
... The potassium ion channel from the prokaryotic soil bacterium
Streptomyces lividans is an integral membrane protein with
sequence similarity to all known potassium ion channels,
particularly in the pore region. ... ... Doyle et al (8 authors
at Rockefeller University, US) report an x-ray analysis (data to
3.2 angstroms) of the Streptomyces lividans potassium channel
reveals four identical subunits create an inverted cone cradling
the selectivity filter of the pore in its outer end. The narrow
selectivity filter is only 12 angstroms long, whereas the
remainder of the pore is wider and lined with hydrophobic amino
acids. The selectivity filter is apparently held open by
structural constraints to coordinate potassium ions but not
smaller sodium ions. The authors suggest the architecture of the
pore establishes the physical principles underlying selective
potassium ion conduction.
-----------
SCI 1998 3 Apr
SW 1998 17 Apr 98
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SCIENCE-WEEK 5 Oct 2001 http://scienceweek.com
-------------------
Related Background:
SIMILAR STRUCTURE OF PROKARYOTIC VS. EUKARYOTIC K(+) CHANNELS
Toxins from scorpion venom are known to interact with potassium
ion channels in eukaryotic cell membranes. Mackinnon et al (5
authors at Rockefeller University, US) report the use of resin-
attached mutant potassium ion channels from the bacterium
Streptomyces lividans to screen scorpion venom, and the toxins
that interact with the channel were identified by mass
spectrometry. The authors suggest their results indicate that the
prokaryotic potassium ion channel, whose structure has now been
revealed, has the same pore structure as eukaryotic potassium ion
channels, and that this structural conservation, through the
application of their techniques, offers a new approach to
potassium ion channel pharmacology.
-----------
SCI 1998 3 Apr
SW 1998 17 Apr
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5. ORIGIN OF BIOLOGICAL NITROGEN FIXATION
R. Navarro-Gonzalez et al (University of Mexico, MX) discuss the
geologic history of nitrogen fixation. Nitrogen is an essential
element for life and is often the limiting nutrient for
terrestrial ecosystems. Since most nitrogen is locked in the
kinetically stable form N(sub2) in the Earth's atmosphere,
processes that can fix nitrogen into biologically available forms
-- such as nitrate and ammonia -- control the supply of nitrogen
for organisms. On the early Earth, nitrogen is believed to have
been fixed abiotically as nitric oxide formed during lightning
discharge. The advent of biological nitrogen fixation suggests
that at some point the demand for fixed nitrogen exceeded the
supply from abiotic sources, but the timing and causes of the
onset of biological nitrogen fixation remains unclear. The
authors report an experimental simulation of nitrogen fixation by
lightning over a range of Hadean (4.5 to 3.8 billion years ago)
and Archaean (3.8 to 2.5 billion years ago) atmospheric
compositions, from predominantly carbon dioxide to predominantly
dinitrogen (but always without oxygen). The results suggest that
as atmospheric carbon dioxide decreased over the Archaean period,
the production of nitric oxide from lightning discharge decreased
by two orders of magnitude until about 2.2 billion years ago.
After this time, the rise in oxygen (or methane) concentrations
probably initiated other abiotic sources of nitrogen. The authors
suggest that although the temporary reduction in nitric oxide
production may have lasted only 100 million years or less, this
was potentially long enough to cause an ecological crisis that
triggered the development of biological nitrogen fixation.
-----------
NAT 2001 412:61
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6. MOLECULAR EVOLUTION OF PROTEINS
P. Baudouin-Cornu et al (CNRS, FR) discuss the evolution of the
atomic composition of proteins. A widely accepted principle is
that protein evolution is mainly determined by constraints on
activity, specificity, folding, and stability or protein
molecules. But other constraints come into play, in particular
nutritional constraints, which have thus far received little
attention. The elements used in the construction of proteins are
not only funneled through metabolic pathways but are also subject
to geochemical cycles at the surface of the Earth, so that
metabolic flows and geochemical budgets might be constraints that
were imprinted on protein evolution. To assess the hypothesis
that nutritional constraints might have influenced the evolution
of protein structure, the authors computed the atomic composition
of enzymes involved in elemental assimilation processes in the
two model microorganisms E. coli (a bacterium) and S. cerevisiae
(a yeast). The authors report their results conclusively
demonstrate the systematic occurrence of atomic biases in
assimilatory proteins of these two highly divergent
microorganisms. This suggests that the elemental composition of
biological polymers has been more generally subjected to
ecological constraints than was previously thought, and that
metabolic costs are among the variables optimized by natural
selection. A simple explanation for the biases is that the
chemical structure of proteins performing the assimilation of a
given element should evolve so as to respond to a sudden and
transitory shortage by incorporating the smallest amount of that
element.
-----------
SCI 2001 293:297
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7. HISTORY OF SCIENCE: LAZZARO SPALLANZANI
Paolo Mazzarello (University of Pavia, IT) discusses Lazzaro
Spallanzani (1729-1799). Spallanzani, a Roman Catholic priest,
was professor of natural history at the University of Pavia and a
member of the Royal Society of London. One of Spallanzani's many
experiments was the "real resurrection after death" of small
desiccated animals (Rotifera and Tardigrada) by means of
subsequent humidification. In other experiments, Spallanzani
disproved the doctrine that microscopic life could arise from
spontaneous generation, a theory advocated by another Roman
Catholic clergyman and member of the Royal Society, John
Turberville Needham (1713-1781). The two priests engaged in an
intellectual battle that lasted many years and that ended with
Spallanzani's views prevailing. A fanatical researcher,
Spallanzani carried out what were at that time extremely
audacious experiments. Keeping a female poodle segregated until
it was on heat, Spallanzani artificially inseminated the poodle
with semen obtained from a male poodle. He cut the head off a
snail and observed its capacity to regenerate. He blinded bats,
discovered that their ability to orientate themselves did not
diminish, and thus suspected the existence of a new sense in
these animals. To dissociate the mechanical from the chemical
phenomenon of digestion, Spallanzani swallowed little perforated
wooden tubes or small cloth sacks containing bread or meat. Using
gastric juices obtained from dissected animals and from himself
by induced vomiting, Spallanzani achieved an artificial digestion
of meat and vegetables, thus disproving the prevailing idea of
the existence of a "vital force" in the process. Spallanzani was
the first to observe blood leukocytes, to prove the animal nature
of marine sponges, to demonstrate the respiratory process in many
tissues (not only in the lung, as proposed by Lavoisier). A
polymath, Spallanzani made original observations in many other
fields of science, from mineralogy to volcanology, from chemistry
to oceanography.
-----------
NAT 2001 411:639
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8. SMALL-MOLECULE BINDING TO RNA
C. Karan and B.L. Miller (University of Rochester, US) discuss
the binding of small molecules to RNA. Small molecules that bind
RNA are of exceptional importance as fundamental guides to
understanding molecular recognition, as tools for sequence and
tertiary-structure-selective modification and mapping, and as
potential new therapeutic agents. The majority of RNA-binding
small molecules identified to date are aminoglycoside natural
products, or compounds based on the aminoglycosides. While
efforts by a number of groups to identify novel RNA-binding
compounds have produced several notable successes, selectivity
for RNA over binding to homologous DNA sequences has rarely been
demonstrated. The technique of "dynamical combinatorial
chemistry" employs a mixture of compounds formed under conditions
of thermodynamic equilibrium. Placing such a dynamic
combinatorial library in solution with a target receptor causes
this equilibrium to shift based on the binding energies of the
individual library members, since those that bind the tightest
are removed from the main pool of compounds in solution. In
essence, this is a form of templated synthesis in which the
receptor templates the synthesis of its own ligand. The authors
report the extension of this methodology to RNA binding.
Salicylamides were selected as the ligands for construction of an
RNA-binding library, since these ligands would provide both
metal-binding functionality and a variable position for
incorporation of potential RNA-binding moieties. The authors
report the combinatorial selection of a specific salicylamide
that binds an RNA *hairpin domain with high affinity and with
extraordinary selectivity relative to a homologous DNA hairpin.
The authors suggest these experiments indicate that dynamic
combinatorial libraries will be generally useful for the
identification of novel RNA-binding compounds.
-----------
JACS 2001 123:7455
-----------
Notes:
... ... *hairpin: In this context, the term "hairpin" refers to a
turning of a polymer chain, the turning having the shape of
hairpin.
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SCIENCE-WEEK 5 Oct 2001 http://scienceweek.com

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9. STABILIZATION OF PROTEIN HELICES
B.S. Kinnear and M.F. Jarrold (Northwestern University, US)
discuss helix formation in peptides. Understanding the factors
that stabilize alpha-helices is critical to understanding protein
folding. Structure and sequence information for naturally
occurring proteins has revealed a preference for certain amino
acids in alpha-helices, and thus many studies have focused on the
individual effects of the amino acids on alpha-helix stability,
with algorithms developed that can predict helix content. *Monte
Carlo simulations have indicated that side chain entropy opposes
helix formation, and such simulations can account for most of the
differences in the helix-stabilizing/destabilizing effects of the
natural amino acids. Specifically, side-chain entropy predicts a
helix propensity scale with alanine > leucine > valine. The main
complication in solution studies of alpha-helix stability is that
the solvent environment can change the helix-
stabilizing/destabilizing tendencies of the amino acids. Factors
such as the solvation of the helix backbone may also play a role
in the ability of a particular amino acid to stabilize an alpha-
helix in solution. By studying unsolvated peptides, the intrinsic
factors leading to alpha-helix stability can be elucidated. The
authors report on the conformations of unsolvated leucine-based
peptides, and the results indicate that leucine forms helices
more readily than alanine but less readily than valine. This
suggests that side-chain entropy is not the determining factor in
helix formation in unsolvated peptides. *Molecular dynamics
simulations suggest that the controlling factor is the stability
of the globular state (a compact 3-dimensional geometry):
residues that make poor (high-energy) globules are good at making
helices.
-----------
JACS 2001 123:7907
-----------
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.
... ... *Molecular dynamics simulations: Contemporary molecular
dynamics simulations, which are extrapolations of statistical
mechanics and which originate in the work of Alder and Wainright
in the 1960s, are computer simulations of molecular systems
typically involving hundreds or sometimes thousands of idealized
particles interacting with physically realistic potentials. Such
molecular dynamics simulations can provide time-dependent
properties of a liquid, but most commonly they are used to
produce a set of configurations and forces which can be averaged
to give equilibrium properties of the system.
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10. LEAF SENSORS FOR PALEOCLIMATE CARBON DIOXIDE
Gregory J. Retallak (University of Oregon, US) discusses the
geologic record of atmospheric carbon dioxide. To understand
better the link between atmospheric carbon dioxide concentrations
and climate over geological time, records of past carbon dioxide
are usually reconstructed from geochemical proxies. Although
these records have provided a broad picture of carbon dioxide
variation throughout the Phanerozoic eon (the past 570 million
years), inconsistencies and gaps remain that still need to be
resolved. The author presents a continuous 300-million-year
record of *stomatal abundance from fossil leaves of four genera
of plants that are closely related to the present Ginkgo tree.
Using the known relationship between leaf stomatal abundance and
growing season carbon dioxide concentrations, the author
reconstructs past atmospheric carbon dioxide concentrations. For
the past 300 million years, only two intervals of low carbon
dioxide are suggested by the data, with both intervals coinciding
with known ice ages in the *Neogene and early *Permian eras. But
for most of the Mesozoic era (65 to 245 million years ago),
carbon dioxide levels were high, with transient excursions to
even higher carbon dioxide concentrations. The author suggests
these results are consistent with some reconstructions of past
carbon dioxide and paleotemperature records, but the data
indicate that carbon dioxide reconstructions based on carbon
isotope proxies may be compromised by episodic outbursts of
isotopically high methane. The author suggests the results
support the role of water vapor, methane, and carbon dioxide in
greenhouse climate warming over the past 300 million years.
-----------
NAT 2001 411:287
-----------
Notes:
... ... *stomatal: "Stoma" are pores in the skin (epidermis) of a
leaf or stem of a vascular plant. The stoma are of variable
aperture, the aperture controlled by surrounding cells and
providing regulated gas exchange between the tissues of the plant
and the atmosphere.
... ... *Neogene: The time-frame 23.3 to 1.64 million years ago.
... ... *Permian: The time-frame 290 to 245 million years ago.
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11. HYDROPHOBIC MOLECULAR INTERACTIONS
T.M. Raschke et al (Stanford University, US) discuss theoretical
studies of hydrophobic molecular interactions. The hydrophobic
interaction, the tendency for nonpolar molecules to aggregate in
solution, is a major driving force in biology, a force that
stabilizes biological structures ranging from native
conformations of proteins to cellular membranes, and the origin
of this effect has been the topic of much investigation, both
experimental and theoretical. In a direct approach to the
physical basis of the hydrophobic effect, the authors performed
nanosecond molecular dynamics simulations on increasing numbers
of hydrocarbon solute molecules in water-filled boxes of
different sizes. The intermittent formation of solute clusters
gives a free energy that is proportional to the loss in exposed
molecular surface area with a constant of proportionality of 45
+- 6 calories per mole per square angstrom. The molecular surface
area is the envelope of the solute cluster that is impenetrable
by solvent and is somewhat smaller than the more traditional
solvent-accessible surface area, which is the area transcribed by
the radius of a solvent molecule rolled over the surface of the
cluster. When a factor relating molecular surface area to solvent
accessible surface area is applied, the proportionality constant
is 24 calories per mole per square angstrom. The authors suggest
this is the first direct calculation of the hydrophobic
interaction from molecular dynamics simulations, and that the
excellent qualitative and quantitative agreement with experiment
demonstrates that simple van der Waals interactions and atomic
point-charge electrostatics account for the most important
driving force in biology.
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PNAS 2001 98:5965
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12. ON FLAVOR-SWITCHING OF SOLAR NEUTRINOS
John H. Bahcall (Institute for Advanced Study Princeton, US)
discusses the recent experimental observations that have
apparently solved the long-standing solar neutrino puzzle.
Neutrinos are unique subatomic particles, having no electric
charge, traveling essentially at the speed of light, and existing
in three types ("flavors"): electron neutrinos, muon neutrinos,
and tau neutrinos. These particles are so elusive that one does
not notice the hundred billion solar neutrinos that pass through
one's thumbnail every second. The "solar neutrino mystery" began
in 1968, when a pioneering experiment found fewer electron-type
solar neutrinos than predicted by a detailed model of the Sun
that provides a quantitative estimate of how many neutrinos
should be detected. Two ideas were widely discussed: either the
model of the Sun was wrong, or something happens to the neutrinos
on their way to Earth. In the 1980s and 1990s, a range of
experiments provided circumstantial evidence that some solar
neutrinos change en route to the Earth from the electron-type
produced by the Sun to another type harder to detect. But there
was no evidence for such particle changes, usually called
"neutrino oscillations". This situation changed dramatically in
June 2001, when researchers at the Sudbury Neutrino Observatory
(CA) provided hard evidence that some solar neutrinos do change
type when traveling from the core of the Sun to the Earth.
Arguably, the most spectacular result of this experiment is that
the total number of solar neutrinos measured is approximately
that predicted by the standard solar model, and that is
considered a triumph for the current theory of stellar evolution.
-----------
NAT 2001 412:29
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SCIENCE-WEEK 5 Oct 2001 http://scienceweek.com
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Related Background:
MISSING NEUTRINOS RIDDLE APPARENTLY SOLVED
The neutrino was first theoretically postulated by Wolfgang Pauli
(1900-1958) in 1930 in order to maintain the conservation of
energy principle in the analysis of the results of certain beta-
decay experiments. The Pauli neutrino was a particle with no
charge and zero rest mass. Experimentally, the particle was
tentatively identified by F. Reines and C. Cowan in 1953 and more
definitely in 1956. One of the best sources of neutrinos should
be the nuclear reactions in our own Sun. At the present time, the
fluxes of solar neutrinos measured by various detector
installations have been no more than 60% of that predicted by
theory, and the deficits are a puzzle. In the Standard Model in
particle physics, there are 6 particle types categorized as
leptons: the electron, the muon, the massive tau lepton, and a
neutrino associated with each of these (denoted as 3 neutrino
"flavors" or "generations"). The apparent solar neutrino deficit
could be explained if some electron neutrinos were changing into
tau or muon neutrinos en route to Earth, since neutrino detectors
are particularly sensitive to electron neutrinos. Now the Sudbury
Neutrino Observatory in Canada, a joint venture of Canada, the
US, and the UK, has apparently solved the puzzle by accurately
measuring the flux of electron neutrinos reaching the Earth. By
comparing this flux with those measured by the other more general
neutrino detectors, the Sudbury team concludes that some electron
neutrinos emitted by the Sun are indeed switching flavors.
NAT 2001 411:877
SW 2001 10 Aug
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SCIENCE-WEEK 5 Oct 2001 http://scienceweek.com
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Related Background:
HISTORY OF PHYSICS: THE NEUTRINO
     The history of particle physics during the first 30 years of
the 20th century is an excellent example of the intimate
interplay between theory and experiment. One of the central
problems in the physics of matter during this period was to
understand the emissions of radioactive substances first
discovered in 1896 by Henri Becquerel (1852-1908). Spontaneous
radioactive decay is essentially a spontaneous transmutation of
an unstable atomic nucleus (nuclide) A into nuclide B, with
nuclide A initially in a higher energy state and losing energy to
transmute into the "daughter" nuclide B. During the early years
of particle physics, the energy loss was considered to be
accomplished by emission of one of three types, depending on the
nature of nuclide A: positively charged alpha particles (helium
nuclei), negatively charged beta particles (electrons), or
neutral gamma rays (high energy electromagnetic radiation). Since
the energies of decaying nuclides and daughter nuclides are fixed
according to nuclide identity, one would expect the observed
energies of the 3 types of particles to also be fixed for each
species of decaying nuclide. During the period before 1927, this
was known to be true for alpha particles and gamma rays, but
there was intense controversy about whether it was true for beta
particles. Indeed, some early experiments indicated that it was
not true for beta particles, and this posed a problem, since
conservation laws require an accounting for all the energy and
the numbers for beta decay did not add up. The controversy
continued for nearly 30 years, particularly among
experimentalists who disagreed concerning experimental methods
and interpretations of experimental results, until finally in the
late 1920s it was conclusively demonstrated by experiment that
during the beta-decay process high-speed electrons of various
energies are emitted with a continuous beta-emission energy
distribution spectrum (i.e., a plot of the number of electrons
vs. energy of these electrons) over the range of energies.
     Given the experimental evidence of a continuous beta-decay
spectrum, theoreticians tackled the problem of accounting for
beta decay without violating conservation laws. In 1930, 
Wolfgang Pauli (1900-1958) proposed that when a beta particle was
emitted, another particle, without charge, and perhaps without
mass, was also emitted, and that this second particle carried off
the missing energy. Enrico Fermi (1901-1954) suggested the
particle carrying the missing energy be called "neutrino", which
is Italian for "little neutral one", and in 1934 Fermi
incorporated the neutrino into his theory of beta decay.
     Most theoretical and experimental physicists immediately
accepted the proposed existence of the neutrino as the best
solution to an important puzzle, but it was not until 1956 that
Frederick Reines (1918-1998) and Clyde Cowan (1919-1974) managed
to finally obtain experimental evidence for the existence of the
elusive neutrino by means of experiments involving emission beams
from a fission reactor. Enrico Fermi received the Nobel Prize in
Physics in 1938; Wolfgang Pauli received the Nobel Prize in
Physics in 1945; and Frederick Reines received the Nobel Prize in
Physics in 1995. (Clyde Cowan was not eligible for the Nobel
Prize at the time it was awarded to Reines, since the Nobel Prize
is not awarded posthumously.) 
... ... Allan Franklin (University of Colorado Boulder, US)
presents an essay on the history of beta decay and the neutrino
1900-1930. The author points out there were two major responses
to the establishment of the continuous energy spectrum of beta
decay. One idea, favored by Niels Bohr (1885-1962), was that
energy might not be conserved in beta decay. But work on the
*Compton effect provided evidence against this view. The second
major response was Pauli's "desperate way out", Pauli suggesting
that a very light, neutral particle was also emitted in the beta
decay. Pauli originally called this particle the "neutron", but
Fermi christened the particle the "neutrino" and quickly
incorporated the neutrino into a successful theory of beta decay.
During the next few decades, Fermi's theory was strongly
supported by experimental observations, and that success provided
most physicists with sufficient evidence for the existence of the
neutrino. As stated by Frederick Reines, for 26 years before the
existence of the neutrino was experimentally demonstrated, "the
[Fermi] theory was so attractive in its explanation of beta decay
that belief in the neutrino as a 'real' entity was general."
-----------
Editor's note: Although modern views of beta decay and the
neutrino (see related background material below) are more complex
than the views held in the early years of the 20th century, a
remarkable group of early experimental and theoretical particle
physicists (only some of whom are mentioned in this SW brief)
provided the foundation that still supports our understanding of
the atomic nucleus and radioactive decay.
-----------
PT 2000 February
-----------
Notes:
... ... *Compton effect: (Compton scattering) In general, the
reduction in the energy of high energy photons when the photons
are scattered by free electrons, the electrons thereby gaining
energy, with total energy conserved. The effect was discovered in
1923 by A.H. Compton (1892-1962). Compton received the Nobel
Prize in Physics in 1927.
-------------------
SW 2000 5 May
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SCIENCE-WEEK 5 Oct 2001 http://scienceweek.com
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Related Background:
ON NEUTRINO OSCILLATIONS
The fundamental particles of 20th century physics came into
existence as theoretical constructions designed to explain
certain specific experimental observations. In some cases, the
existence of a particular particle has been verified by direct
experiment; in other cases, the required verification experiments
are extremely difficult to accomplish, and the particles related
to these experiments have remained theoretical constructions.
The neutrino was first theoretically postulated by Wolfgang Pauli
(1900-1958) in 1930 in order to maintain the conservation of
energy principle in the analysis of the results of certain *beta-
decay experiments. The Pauli neutrino was a particle with no
charge and zero rest mass. Experimentally, the particle was
tentatively identified by F. Reines and C. Cowan in 1953 and more
definitely in 1956. Neutrinos are "leptons", which are a group of
point-like particles with *spin of 1/2 that are not affected by
so-called "*strong interactions" and that are not constructed of
*quarks. In the *Standard Model in particle physics, there are 6
particle types categorized as leptons: the electron, the *muon,
the massive *tau lepton, and a neutrino associated with each of
these (denoted as 3 neutrino "flavors" or "generations"). 
Neutrinos are produced in great numbers by the Sun, but they
almost never interact with atoms, and an estimated 10^(12) solar
neutrinos flow through our bodies each second without any
consequence. Measurements of solar neutrinos, however, have
produced a mystery: the neutrino density measured by detectors is
approximately one-third that expected from theoretical
calculations of solar neutrino emission. Two kinds of solutions
have been proposed to resolve this mystery, one solution
involving revisions to the theory of stellar structure, and the
other solution involving revisions to nuclear particle theory. In
the latter case, the proposal is that the neutrino may oscillate
among the 3 different flavors (states), with the result that
neutrino detectors detect only one flavor or one-third of the
solar emission. The existence of such neutrino oscillation would
have important implications, since it has been believed that
neutrinos, like photons, have zero mass. But theory indicates
that if neutrinos oscillate they must have mass, and neutrinos
are so numerous that even an extremely small mass would
theoretically be sufficient to affect the future of the Universe
as a whole. The question of neutrino oscillation, therefore, is a
critical problem affecting a good deal of fundamental physics and
cosmology, and there is recent evidence interpreted to indicate
that such oscillation does indeed occur and that neutrinos do
indeed have nonzero mass.
... ... K. Kaneyuki and K. Scholberg (2 installations, JP US)
present a detailed review of current research concerning neutrino
oscillations, the authors making the following points:
     1) The basic strategy for measuring neutrino oscillations is
simple. Given a source of neutrinos, either natural or
artificial, one allows the neutrinos to propagate for a known
distance, and then one obtains as much quantitative information
as possible concerning their energy and flavor. If the amount of
a given flavor, as a function of energy and distance, is that
expected from the quantum mechanical predictions arising from the
oscillation hypothesis, then neutrino oscillation has been
discovered.
     2) Three neutrino sources are currently used in research:
The Sun, atmospheric *cosmic-ray showers, and particle
accelerators. At present, the clearest neutrino oscillation
evidence from atmospheric neutrinos comes from the "Super-
Kamiokande" experiment, which observes neutrino interactions by
detecting *Cherenkov (Cerenkov) radiation. The Super-Kamiokande
experiment has been built and operated by a collaboration of
approximately 130 scientists from Japan and the US, the project
headed by Y. Totsuka (University of Tokyo, JP). The apparatus
consists of 50 kilotons of ultrapure water housed approximately
one kilometer underground in the Kamioka mine in Japan. The
detector consists of 2 concentric cylinders 40 meters high and
with an outer radius of 20 meters. The inner cylinder contains
11,146 inward-facing photomultiplier tubes, each 50 centimeters
in diameter. These photomultiplier tubes detect Cherenkov
radiation from particle interactions inside the inner cylinder
(which contains the ultrapure water). The outer cylinder has 1885
20-centimeter-diameter photomultiplier tubes facing outward to
check for non-neutrino related Cherenkov radiation from entering
charged particles (cosmic-ray muons and radioactivity). Super-
Kamiokande began operation on April 1, 1996.
     3) The essential basis of the Super-Kamiokande experiment is
as follows: When a high-energy cosmic-ray particle (e.g., a
proton) hits an atomic nucleus in the upper atmosphere, the
collision produces a shower of secondary particles. Some of these
particles decay to other particles, some of which are neutrinos.
Most of the charged particles produced in the shower lose energy
as they move through the atmosphere and into the Earth's surface.
Neutrinos, however, because of their extremely small rate of
interaction, pass through the atmosphere and the ground, the vast
majority penetrating to the other side of the Earth. But a few
neutrinos do interact (e.g., with the ultrapure water in the
Super-Kamiokande reservoir), and the Super-Kamiokande apparatus
can detect the interaction of approximately 8 neutrinos per day
in its inner volume.
     4) The authors conclude: "These are exciting times for
neutrino physics, and for elementary particle physics as a whole.
The atmospheric neutrino data fit the neutrino-oscillation
hypothesis beautifully, and this verification that at least some
neutrinos have mass is an enormous step forward: It is the first
clear indication of physics beyond the Standard Model."
-----------
AS 1999 87:222
-----------
Notes:
... ... *beta-decay: A type of interaction in which an unstable
atomic nucleus changes into a nucleus of the same mass number but
different proton number. The change involves the conversion of a
neutron into a proton with the emission of an electron and an
electron *antineutrino, or of a proton into a neutron with the
emission of a positron and an electron neutrino. The electrons or
positrons emitted are called "beta particles". (Positrons are
electron antiparticles. See *antineutrino.)
... ... *antineutrino: An antiparticle (antimatter) is a
subatomic particle that has the same mass as another particle and
equal but opposite values of some other property or properties.
For example, the antiparticle of the electron is the positron. An
antineutrino, the antiparticle to the neutrino, has zero mass,
*spin 1/2, and positive helicity. There are 2 antineutrinos, one
associated with the electron and one associated with the *muon.
... ... *spin: In quantum mechanics, "spin" is the intrinsic
angular momentum of a subatomic particle. Spin states are
quantized, multiples of h/2ã, where h = Planck's constant, and
each particle is characterized by a quantum spin number which is
the multiple factor.
... ... *strong interactions: According to the *Standard Model,
the fundamental forces comprise the gravitational force, the
electromagnetic force, the nuclear strong force, and the nuclear
weak force.
... ... *quarks: A quark is a hypothetical fundamental particle,
having charges whose magnitudes are one-third or two-thirds of
the electron charge, and from which the elementary particles may
in theory be constructed.
... ... *Standard Model: In particle physics, the Standard Model
is a theoretical framework whose basic idea is that all the
visible matter in the universe can be described in terms of the
elementary particles leptons and quarks and the forces acting
between them.
... ... *muon: The 3 leptons (electron, muon, tau) differ from
each other only in mass. The muon is 200 times more massive than
the electron.
... ... *tau: (tauon) The mass of the tau particle is 3560 times
the mass of the electron.
... ... *cosmic-ray: Cosmic rays are highly energetic particles
moving at close to the speed of light and continuously bombarding
the Earth's atmosphere from all directions. The energies of the
particles are enormous and range from 10^(8) to over 10^(19)
electronvolts.
... ... *Cherenkov (Cerenkov) radiation: Discovered in 1934 by
Cerenkov (1904-1990), Cerenkov radiation is electromagnetic
radiation, usually bluish light, emitted by a beam of high-energy
charged particles passing through a transparent medium at a speed
greater than the speed of light in that medium. The radiation is
essentially a shock wave, the effect analogous to that of a sonic
boom.
-----------
SW 1999 25 Jun
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SCIENCE-WEEK 5 Oct 2001 http://scienceweek.com
-------------------
Related Background:
THEORETICAL IMPLICATIONS OF NEUTRINO DEFICITS
Leptons are a class of point-like fundamental particles showing
no internal structure and no involvement with the strong forces.
There are 6 leptons: the electron, the muon, the massive tau
lepton, and a specific neutrino associated with each of the
former (3 neutrino "flavors"). An antilepton is an anti-particle
of a lepton, for example an antineutrino (an anti-particle of a
neutrino) or a positron (an anti-particle of an electron). The
term "lepton-number" refers to a conserved quantum number equal
to the number of leptons minus the number of antileptons in a
system, with the lepton-number conservation laws separately
individualized for each flavor. Neutrinos have zero charge,
possibly zero mass, and an angular momentum factor (spin) of 1/2.
Various processes produce neutrinos: stellar nuclear reactions,
reactions occurring during supernova explosions, cosmic ray
collisions with matter, etc., and installations have been
constructed to measure the flux of neutrinos impacting Earth. To
avoid contamination by cosmic rays, such installations are deep
underground. One such installation is the Kamioka mine in Japan,
which houses the Kamiokande detector, an emplacement of a large
volume of ultrapure water. One of the best sources of neutrinos
should be the nuclear reactions in our own Sun. At the present
time, the fluxes of neutrinos measured by various detector
installations have been no more than 60% of that predicted by
theory, particularly in the case of solar neutrinos, and the
deficits are a puzzle. One possibility is that since current
detectors measure only one lepton flavor, the deficits may be a
result of neutrinos oscillating (converting) from one flavor to
another, which would imply neutrinos have mass. Another
possibility is that there is something wrong with the current
theory of stellar nuclear reactions or with the current theory of
fundamental particles. ... ... F. Wilczek (Instit. for Advanced
Study Princeton, US), reviewing discussions at a recent neutrino
conference (Santa Barbara, Calif. US, 2-6 Dec 97), notes the
anomalies and contradictions produced by current neutrino
research, particularly the anomalies in cosmic ray neutrino
flavor ratios reported by the SuperKamiokande detector, and
suggests that it seems probable the separate laws of lepton-
number conservation will soon fall.
-----------
NAT 1998 8 Jan
SW 1998 23 Jan
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SCIENCE-WEEK 5 Oct 2001 http://scienceweek.com

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13. IN FOCUS: ON STATISTICAL REGRESSION 
"What we call regression actually began with the investigations
of the English scientist Sir Francis Galton [1822-1911]... A
cousin of Charles Darwin [1809-1882], Galton had wondered why
there is a tendency in the general population for the children of
taller parents to be shorter than their parents and for the
children of shorter parents to be taller than their parents.
These ponderings led Galton into some of the earliest studies of
what is now known as the science of heredity. The fact that the
children of taller (shorter) parents did not continue to grow
ever taller (shorter) with each succeeding generation alerted
Galton to the notion that there are certain self-corrective
elements in humanity's genetic pool that limit the extreme
heights to which human beings will grow. This is why giants are
not found in great numbers. Although the delineation of these
factors would have to await the arrival of later generations of
medical researchers, Galton was perceptive enough to see that the
population did tend toward a band of average heights. This
realization that there is a fairly narrow range of heights for
humans prompted other fertile minds to consider the ideas that
underpin the concept of regression. Statisticians use regression
lines to identify linear relationships between two variables. The
so-called regression line can be viewed as a graphical 'average'
of all of the different plotted points on a graph. However, the
use of the word 'average' is not really appropriate here, because
we are talking about something other than simply adding up all of
the vertical and horizontal coordinate numbers on a graph and
dividing [the total] by the number of such points. The regression
line is something different. It is the line that minimizes the
differences between all of the points on a graph. Even though no
single point may lie within this line, the regression line
represents what statisticians refer to as the line of least
squares. It is the line that encompasses the least amount of
deviation from each of the plotted points on the graph while
still managing to express a linear relationship between the
variables."
-----------
Jefferson H. Weaver: _Conquering Statistics: Numbers without the
Crunch_
(Perseus Publishing, Cambridge MA 2000, p.212)
http://www.amazon.com/exec/obidos/ASIN/0738204951/scienceweek
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SCIENCE-WEEK 5 Oct 2001 http://scienceweek.com

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14. SW ARCHIVE: 
ON POPULAR CULTURE AND THE THREAT TO RATIONAL INQUIRY
In an essay on current popular attitudes toward science and
scientists, Douglas R. Hofstadter (Indiana University
Bloomington, US) makes the following points: 1) Science is
currently presented to children and teens combined with
irrelevancies such as action-packed stories, rock music, amusing
quipsters, sassy jokes, sexual innuendoes, or up-to-date teen
slang -- as if science is a "bitter pill" that needs sugar-
coating. 2) Society today seems to be pervaded by a deep,
unconscious, anti-science bias. Scientists are represented in
movies, television, and books as heartless, humorless nerds who
would sooner kill than smile, sooner write abstruse formulas than
make love. 3) There is a dismissive attitude toward science as an
explanatory framework for the world, and the welcoming of so-
called "mysteries" such as after-death experiences, alien
abductions, crystal channeling, crop circles, telekinesis,
clairvoyance, extrasensory perception, or remote viewing. 4)
Movie and television viewers and readers of serious literature
are given the tacit message that the line between the natural and
supernatural is blurry, and perhaps even nonexistent. 5) The
general public no longer views science with a sense of awe and
mystery, but instead considers it conservative and mundane,
"trapped" in logical thinking. 6) The implicit message of popular
culture is that science is boring, conservative, closed-minded,
devoid of mystery, and a negative force in society. The author
concludes: "I have no quick fixes. I do not know how to quickly
and easily repair decades of damage. I do not fully understand
why the sands have shifted so radically. All I can do is look on
in sadness and worry about the future of rational inquiry,
bemoaning the loss of awe toward genuine mysteries that our
society was once lucky enough to possess."
-----------
SCI 1998 281:512
SW 1998 14 Aug
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SCIENCE-WEEK 5 Oct 2001 http://scienceweek.com

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15. SOURCES:
AS: Amer. Scientist; CEN: Chem. & Eng. News; GD: Genes & Dev.;
GR: Genome Res.; JACS: J. Amer. Chem. Soc.; JAMA: J. Amer. Med.
Assoc.; JCE: J. Chem. Educ.; MMWR: CDC Morbidity and Mortality
Weekly Report; NAT: Nature; NATM: Nature Medicine; NEJM: New
Engl. J. Med.; NS: New Scientist; NYT: New York Times; NYR: New
York Review; PNAS: Proc. Natl. Acad. Sci.; PRL: Phys. Rev. Lett.;
PT: Physics Today; SA: Scientific American; SCI: Science; SW:
ScienceWeek; TS: The Scientist.

In the text, the affiliation following the author's name is the
affiliation of the lead author. The indication (na) signifies no
known research affiliation.

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