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This Week In "science"

gostya, 02.12.2005 05:59
_______________________________________________________________________
Copyright © 2005 by the American Association for the Advancement of
Science.


This Week in SCIENCE
December 2 2005, 310 (5753)

THIS WEEK IN SCIENCE
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Expedient Cytokine Trafficking
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Phagosomes are formed when cells such as macrophages engulf relatively
large particles, like bacteria, from the external milieu. The source of
membrane involved in the formation of the phagosome and the ability of
other organelles to fuse with the phagosome is a topic of recent
controversy. Murray et al. (p. 1492, published online 10 November) describe
a fundamental and clever adaptation of phagosomal membrane trafficking in
macrophages, whereby recycling endosomes fuse with the newly forming
phagosome to create the site for release of tumor necrosis factor--a
proinflammatory cytokine involved in innate immunity.

CREDIT: SANGERMANI/UNIVERSITY OF QUEENSLAND

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Dating Deep Circulation
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During the transition from the Last Glacial Maximum to the Holocene, a
series of changes in the deep-ocean circulation pattern occurred in the
North Atlantic. Robinson et al. (p. 1469, published online 3 November) made
measurements of the carbon-14 content of the deep-sea coral Desmophyllum
dianthus in order to characterize better the changes in circulation of
intermediate and deep water in the North Atlantic during that transitional
interval. The observed radiocarbon changes in the deep North Atlantic Ocean
are consistent with the "bipolar seesaw" model of deep ocean circulation.
The greater variability in waters at depths of less than 2500 meters
correlates with smaller climate events that occurred near the poles.

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Earlier Oxygen Onset?
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Some microbes use the redox reactions of intermediate sulfur compounds as
an energy source. These compounds originally formed via oxidation
reactions, and thus it has been thought that these microbes evolved after
about 1 billion years ago, when the oxygen content of Earth's atmosphere
increased and caused a distinctive shift in the main sulfur isotopes
(34S/32S) that was recorded in sediments. Johnston et al. (p. 1477) show
that including data for 33S isotope in the analysis provides a more
accurate signal of microbial sulfur disproportionation. The diagnostic
signal emerges considerably earlier than has been thought at about 1.3
billion years ago.

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Long After the Quake
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The extending western margin of the Great Basin is one of the more
seismically active regions of North America, and four large earthquakes
occurred in western Nevada from 1915 to 1954. Gourmelen and Amelung (p.
1473; see the Perspective by Hammond) used radar interferometry to map the
continued deformation of this region during the past 10 years and show that
the region still seems to be responding slowly to these earthquakes.
Consideration of a broad response helps reconcile global positioning
satellite data and imply that much of the highly extended crust to the east
is now behaving rigidly.

CREDIT: GOURMELEN AND AMELUNG

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Mercurial Wetting
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The interiors of carbon nanotubes can be filled by liquids through
capillary action, but the surface tension of liquid metals such as mercury
is too high for the metal to enter the nanotube by this process. Because of
this lack of wetting, mercury has been used to form Ohmic contacts to
carbon nanotubes. Chen et al. (p. 1480) present evidence for mercury
entering open-ended, single-walled carbon nanotubes (SWNTs) by an
electrowetting process that is facilitated by the potential drop created
when the nanotube is used as a contact. Application of a bias potential
changes the force needed to extract the SWNT from a mercury surface, and
postmortem transmission electron microscopy indicates that mercury entered
the interiors of the SWNTs and also wetted the exterior surfaces.

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Bird Heads and Toes
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Archaeopteryx is broadly recognized as the first known bird. It has been
represented by nine specimens dating to about 150 million years ago (Late
Jurassic). However, these nine specimens are all somewhat incomplete,
particularly in important areas of the head and feet. Mayr et al. (p. 1483;
see the news story by Stokstad) now describe a 10th specimen that shows new
features in these important areas. Its first toe is only partially
inverted, and its second can hyperextend. These features, as well as
revealed parts of its skull, are notably similar to proposed theropod
ancestors to birds.

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Heading Off Hearing Impairment
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Congenitally deaf cats and mice show clear abnormalities in the synaptic
structure of auditory nerve endings. Are these abnormalities permanent, or
could early treatment restore their original function? Ryugo et al. (p.
1490) compared normal hearing, congenitally deaf, and congenitally deaf
cats fitted with a cochlear implant system. They investigated anatomical
and functional restoration of the auditory nerve synapses; in particular,
changes in a structure called the endbulb of Held. The artificial
electrical stimulation of the cochlea by the cochlear implant rescued many
of the normal features of this synapse.

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The Matter of Taste
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The sensation of taste is generated in taste buds, which then send the
information through the gustatory nerves to the brain. The neurotransmitter
between the taste buds and the nerve had been thought to be serotonin, but
mice genetically manipulated to lack functional serotonin receptors sense
taste stimuli normally. Finger et al. (p. 1495) have investigated another
candidate neurotransmitter that functions at these synapses, adenosine
triphosphate (ATP). Mice lacking the two ionotropic receptors for ATP (P2X2
and P2X3) did not show responses to taste stimuli in the gustatory nerves.
In addition, these mice could not detect most tastes in behavioral tests in
which they had to show preference for one substance over another. These
results, considered with the release of ATP from taste buds when they are
stimulated, show that ATP is indeed the neurotransmitter at these synapses.
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Chromatin and Stem Cells
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Two stem cell types are found in the Drosophila ovary, germline stem cells
and somatic stem cells. Self-renewal of these cells requires the function
of the Hedgehog, bone morphogenic protein (BMP), and Wingless signaling
pathways. Xi and Xie (p. 1487) now show that two adenosine
triphosphate-dependent chromatin remodeling factors, Imitation SWI (ISWI)
and DOMINO (DOM), also regulate self-renewal in the Drosophila ovary. DOM
is required for somatic stem cell self-renewal and ISWI is required for
germline stem cell self-renewal in response to BMP signaling in the stem
cell microenvironment or "niche." Because this type of chromatin remodeling
complex is highly conserved, it is likely that chromatin remodeling may
play a role in stem cell self-renewal in other organisms.

CREDIT: XI AND XIE

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Colon Cancer Connections
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A previously unrecognized connection between two well-known signaling
pathways appears to provide a crucial mechanism for control of
proliferation of colon cancer cells. Castellone et al. (p. 1504, published
online 17 November) show that the EP2 subtype of prostaglandin E2 receptor
mounts a two-pronged attack that activates a transcriptional program that
favors cell proliferation. When PGE2 binds to EP2, the associated
heterotrimeric guanine nucleotide-binding protein (G protein) is activated.
The G protein and subunits act through distinct pathways that converge to
promote stabilization and nuclear translocation of-catenin, a protein that
promotes transcription of specific genes that increase proliferation of
cancer cells. This signaling system may explain why nonsteroidal
anti-inflammatory drugs, which inhibit signaling through PGE2, can at times
inhibit development of colon cancer in mice and human patients.

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The IgGs Have It
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Different classes of antibody (the immunoglobulins; IgA, IgD, IgE, IgG, and
IgM) perform divergent functions within the immune system. IgG has also
evolved further into subclasses that vary considerably in their potency in
particular types of immune responses. Each IgG subclass possesses a range
of binding affinities for the different inhibitory and activating receptors
that engage the constant Fc region of the antibody molecule. Nimmerjahn and
Ravetch (p. 1510; see the Perspective by Woof) used this observation to
construct antibodies bearing the same antigenic specificity combined with
the subclass-specific portions of Fc. The ability of these hybrid
antibodies to mediate their immunological effects in vivo could be
predicted by the strength with which the Fc portion bound the different
activating or inhibitory Fc receptor (FcR). Thus, the specificity and
strength of FcR binding is a central means by which IgG subclasses
determine their dominance in a particular immune response.

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Keeping Survivin on Target
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Many proteins are involved in the orchestration of the events required for
the successful completion of mitosis. Vong et al. (p. 1499, see the
Perspective by Earnshaw) searched for proteins that interact with survivin,
a protein that functions in regulation of mitosis and accumulates on
condensing chromosomes at the centromeres and later on the spindle. A
deubiquitinating enzyme known as hFAM was identified that appears to
control localization of survivin and its association with other proteins.
Survivin was coupled to ubiquitin through Lys63 linkages, a modification
that influences protein-protein interactions, and this modification was
necessary for proper binding of survivin to centromeres. Preventing
ubiquitination by mutating Lys63 disrupted chromosome alignments and
mitotic progression. Thus, enzymes regulating protein ubiquitination appear
to have key regulatory roles in controlling the dynamic protein
interactions required for proper execution of mitosis.

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Not Lost in Translation
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The mammalian translation factor eIF3 (a complex of about 750 kilodaltons)
prevents premature association of the large and small ribosome subunits; it
is involved in start codon detection; and it assists in the assembly of
active ribosomes. In addition, eIF3 recruits messenger RNA (mRNA) bearing
either a methylated guanosine cap at the 5-end or an internal ribosome
entry site (IRES) to the small subunit of the ribosome. Using cryoelectron
microscopy reconstructions, single-particle analysis, and modeling,
Siridechadilok et al. (p. 1513) now elucidate the structure and
interactions of eIF3. eIF3 interacts with the hepatitis C virus (HCV) IRES
RNA and the 5-cap binding complex eIF4F via the same domain to position the
mRNA strand near the exit site of the 40S ribosomal subunit. This work
provides structural insight for translational regulation by eIF3, including
the prevention of premature ribosome assembly.


_______________________________________________________________________
Copyright © 2005 by the American Association for the Advancement of
Science.
Guest, 10.12.2005 01:07
Copyright © 2005 by the American Association for the Advancement of
Science.

This Week in SCIENCE
December 9 2005, 310 (5754)

THIS WEEK IN SCIENCE
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DNA Twisted into Tetrahedra
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One strategy for building molecular nanostructures in three dimensions is
to exploit the connectivity afforded by nucleic acid structures. In many
cases, the steps needed to select particular base pairing to create
structures such as cubes lead to long, multistep syntheses. Goodman et al.
(p. 1661) have developed a rapid self-assembly process that creates DNA
tetrahedra that have 10 to 30 base pairs on each edge. Four single strands
that contain the complementary sequences for six edges anneal in seconds in
95% yield, and single diastereomeric products are formed. The authors also
present atomic force microscopy studies of the compression of a single DNA
tetrahedron.

CREDIT: GOODMAN ET AL.

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Restoring the Forests
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Deforestation in the tropics has had seriously adverse consequences for
biodiversity, ecosystem services, and the human inhabitants of the tropical
forest. In recent years, projects have been set in motion to restore
degraded forest lands in some countries. Lamb et al. (p. 1628) review the
range of approaches to restoration and assess the extent to which these
approaches might be successful in achieving their aims, particularly with
respect to human well-being.

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Superconducting Qubit Interferometry
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Mach-Zehnder interferometry is a powerful technique to probe quantum
optical effects. Such interferometers contain two beam splitters. The first
sends two beams of photons along separate paths. The acquired path or phase
difference the two beams may acquire creates interference fringes after the
second beam splitter recombines the two beams. Oliver et al. (p. 1653,
published online 10 November) show that a two-level superconducting qubit
can also be made to exhibit similar interference fringes. In this case, the
anti-crossing between the ground and excited states acts as the beam
splitter, and the energy level splitting between them corresponds to the
optical path difference. Multiple photon transitions (up to 20) can be
induced, thus illustrating a potentially useful route for the manipulation
of superconducting qubits in quantum computing schemes.

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Going Softer
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Whether added deliberately or by accident, impurities or solutes have long
been used to strengthen metals. A more recent discovery was that impurities
can soften some metals, but the underlying reasons have not been fully
understood. Using simulations, Trinkle and Woodward (p. 1665; see the
Perspective by Chrzan ) show that for molybdenum, certain transition metal
solutes can influence the energy barriers for dislocation motion, and in
some cases, these changes lead to a softening of the metal. By reducing the
strength, and thus the tendency to fracture abruptly, these modified metals
may find expanded use in structural components.

CREDIT: TRINKLE AND WOODWARD

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Rapid Glacial Erosion
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Determining the relative importance of incision by rivers and glaciers in
the creation of alpine valleys is often hampered by difficulties in
quantifying rates of glacial erosion. Shuster et al. (p. 1668; see the
cover) assessed the timing and rate of glacial erosion by 4He/3He
thermochronometry. Using an example from the Coast Mountains of British
Columbia, Canada, they determined erosion rates both before and during
alpine glaciation. The Klinaklini Valley deepened rapidly by 2 kilometers
or more around 1.8 million years ago when it became glaciated, at least six
times as fast as during its preglacial state.

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Moon Magma
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A giant impact into the early Earth is thought to have ejected a huge
amount of debris into orbit that coalesced to form the Moon. Heat from the
impact also apparently melted much of the Moon and created a huge ocean of
magma. One means of dating these processes is by detecting 182W, the
daughter product of a short-lived isotope, 182Hf. Differences in the
abundances of 182W are produced when magma, rocks, and crystals separate
while 182Hf is still present. Kliene et al. (p. 1671; published online 24
November) report accurate measurements of tungsten isotopes by analyzing
metals returned in Apollo samples (metals provide the most accurate
measure). The data imply that the giant impact occurred about 30 million
years after the formation of the solar system and that the magma ocean had
solidified by about 50 million years.

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Protein Interaction in the Gaseous Phase
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The identification of transient or readily reversible interactions between
proteins is a difficult problem that has been addressed with a variety of
methods. Ruotolo et al. (p. 1658; published online 17 November) have now
applied mass spectrometry to the problem in order to exploit its advantages
of sensitivity and speed. They show that the trp RNA-binding attenuator
protein (TRAP) maintains its 11-membered ringlike structure in the gas
phase and that binding of RNA and tryptophan influences the shape and
stability of the ring in a fashion consistent with its known behavior in
aqueous solution.

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The Liver and the Control of Glucose Metabolism
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The protein kinase and tumor suppressor LKB1 is a potential activator of
the adenosine monophosphate. activated protein kinase (AMPK), a kinase that
senses cellular energy levels by binding the metabolite AMP. Shaw et al.
(p. 1642; published online 24 November) engineered mice so that LKB1
expression could be acutely blocked only in the liver; they found that its
expression plays a critical role in the control of metabolism in the liver
and in glucose homeostasis. In the absence of LKB1, AMPK was almost
completely inactive. Animals lacking LKB1 in the liver showed hyperglycemia
and increased expression of genes encoding enzymes of gluconeogenesis and
lipogenesis.

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Predicting Responses on the Death Pathway
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Multiple signaling pathways can influence whether a cell commits to the
cell death program known as apoptosis. For many years, it has been possible
to categorize signals as contributing to the "gas" or to the "brakes."
However, predicting the biological outcome of multiple signals that apply
some gas here, and a stomp on the brakes there, has remained a challenge.
Janes et al. (p. 1646) applied a systems-level approach to this problem and
created a model to analyze coupling between almost 8000 measurements of
signaling parameters in cultured cells with about 1500 measures of the
various stages of apoptosis in cells treated with various combinations of
cytokines. The model allows the cellular apoptotic response to be correctly
predicted under a variety of conditions.

CREDIT: JANES ET AL.

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Land-Use Effects on Climate
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Climate models are still only rather crude representations of real climate
systems, and one class of important feedbacks not adequately realized in
them is that of land processes. Fedemma et al. (p. 1674; see the
Perspective by Pielke) investigate the role of biogeophysical land
processes, which directly affect the absorption and distribution of energy
at the Earth's surface, by integrating them into a global climate model.
Increases in atmospheric CO2 concentrations during the next century and
associated greenhouse gas-induced warming led to significant regional
impacts directly associated with land cover, mostly in mid-latitude and
tropical areas. However, global average temperature was not affected much
by land cover change because regional variations that led to more or less
warming tended to cancel out.

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Lipids and Neurotoxins
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The venom of certain snakes includes neurotoxins capable of paralyzing
their victims. Upon intoxication, snake presynaptic phospholipase A2
neurotoxins (SPANs) cause motor nerve terminals in the neuromuscular
junction to enlarge and induce exocytosis of neurotransmitters from
synaptic vesicles. Rigoni et al. (p. 1678; see the Perspective by
Zimmerberg and Chernomordik) now find that a mixture of lysophospholipids
and fatty acids, which are released by SPANs acting on phospholipids,
closely mimics all of the biological effects of SPANs. Thus, at the
presynaptic membrane, lysophospholipids and fatty acids help to generate a
membrane conformation that promotes vesicle exocytosis and also inhibits
synaptic vesicle retrieval.

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Ambiguity Averse
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In a 2002 news briefing, U.S. Secretary of Defense Donald Rumsfeld famously
distinguished between known knowns, known unknowns, and unknown unknowns.
The last group remains difficult to discuss, but neuroscientists and
economists have joined forces to examine the distinctions between the first
two. Hsu et al. (p. 1680; see the Perspective by Rustichini) challenged
subjects to choose between risky and ambiguous payoffs, where the former
type of choice contains outcomes with known probabilities and the latter
type features the same outcomes but with unknown probabilities. Even under
conditions where the expected payoffs are equal, normal humans prefer risk
over ambiguity, and brain-imaging results suggest that the amygdala and
orbitofrontal cortex (OFC), which both become more active with ambiguity,
modulate a third area of the brain, the striatum. Notably, patients bearing
lesions in the OFC did not exhibit an aversion to ambiguity.

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Checkpoint for Synapsis
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The complex mechanics of the eukaryotic cell cycle is monitored at a number
of points to ensure that everything is going according to plan, before the
next step in the process is executed. Known checkpoints include DNA
replication, DNA damage, and spindle function. Bhalla and Dernburg (p.
1683) identify a checkpoint that monitors synapsis, or pairing between
homologous chromosomes during the meiotic (haploid gamete-producing) cell
cycle in Caenorhabditis elegans, which ensures the accurate chromosome
segregation during division. The checkpoint requires chromosomal sites
known as pairing centers, where synapsis initiates, and is distinct from
the DNA damage checkpoint monitoring meiotic recombination. The checkpoint
involves the PCH2 gene, which is also involved in the pachytene checkpoint
in budding yeast.

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Getting to Grips with G Protein Structure
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Heterotrimeric G protein signaling is important in a wide range of
physiological processes; however, little is known about how activated
heterotrimer subunits (G) are oriented at the membrane during signal
transduction. Tesmer et al. (p. 1686) provide a snapshot of activated G
proteins in a 3.1 angstrom crystal structure of G protein-coupled receptor
kinase 2 (GRK2) bound simultaneously to activated Gq and G. GRK2 is
critical to the phosphorylation-dependent desensitization of many G
protein-coupled receptors. In the complex, Gq is fully disassociated from
G, oriented away from its position in the heterotrimer, and forms an
effector-like interaction with GRK2.

_______________________________________________________________________
Copyright © 2005 by the American Association for the Advancement of
Science.

gostya
Guest, 16.12.2005 23:15
_______________________________________________________________________
Copyright © 2005 by the American Association for the Advancement of
Science.

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This Week in SCIENCE
December 16 2005, 310 (5755)

THIS WEEK IN SCIENCE
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Comparing Correlations
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Quantum mechanics offers an exact solution to the forces binding an
electron to a proton in the hydrogen atom. However, adding just one more
proton and electron to the system presents an intractable complication
arising from the correlated motion of the electrons. Vanroose et al. (p.
1787) have improved the approximate solution by numerical computation. They
analyze the trajectories of both electrons upon double ionization of the
hydrogen molecule by a single photon, specifically focusing on the
influence of changing the internuclear separation. The result is distinct
from the path taken on double ionization of the helium atom, These findings
indicate that significant correlation effects stem from a molecular
geometry (an electron pair shared between two protons), as opposed to an
atomic geometry (an electron pair symmetrically surrounding two protons).

CREDIT: VANROOSE ET AL.

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Begin with a Backflip
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The initiation of diffusion of molecules on surfaces is mainly thought of
in terms of translational motion. Backus et al. (p. 1790, published online
10 November; see the Perspective by Ueba and Wolf) followed the diffusion
of CO molecules on a stepped Pt surface with ultrafast vibrational
spectroscopy by using changes in CO stretching frequencies to distinguish
different adsorption sites. Photoexcitation of the CO with a laser pulse
revealed very fast motion (a time constant of only 500 femtoseconds) that
was associated with CO rotation rather than translation. Density functional
theory calculations show that the excitation of frustrated rotational
motion of the CO molecule is needed for the molecule to hop to an adjoining
adsorption site.

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The Reptile-Dinosaur-Bird Conundrum
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Examination of the histology of fossil bones has shown that most dinosaurs,
like birds and mammals today, attained their adult size at about the same
age after a period of rapid growth, independently of environmental factors.
In contrast, many reptiles adjust their growth in response to temperature
and other factors, and may attain adult size at rather different ages. By
examining a large collection of fossils from central Europe, Sander and
Klein (p. 1800; see the news story by Gramling) now show that the most
common Triassic dinosaur, the large prosauropod Plateosaurus engelhardti
grew more like turtles, snakes, and alligators, unlike later dinosaurs,
whose growth response resembles that of birds and mammals.

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Small Reactors
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Positron emission tomography (PET) achieves local sensitivity in medical
imaging of organs by detecting the emissive decay of isotopically unstable
molecular probes. This instability also requires the rapid and efficient
synthesis of probe compounds. Lee et al. (p. 1793) have built a
computer-controlled device, roughly the size of a penny, for optimizing the
speed and cost of such preparations. The micrometer-scale valves and
channels achieve rapid mixing and solvent exchange, and efficient heat
transfer, as demonstrated in the multistep synthesis of 18F-radiolabeled
2-deoxy-2-fluoro-D-glucose, the most widely used PET probe.

CREDIT: LEE ET AL.

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The Genetics of Skin Pigmentation
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Little is known about the specific genes that contribute to the variations
in human skin color. An exciting clue has now emerged from an unlikely
source, a tiny aquarium fish. Working with a mutant line of zebrafish
called golden, whose stripes are paler than those in wild-type fish,
Lamason et al. (p. 1782; see the cover and the news story by Balter) found
that the altered pigmentation was caused by a mutation in the slc24A5 gene,
which encodes a protein potentially involved in cation exchange. The gene
is highly conserved in vertebrates, and expression of the human gene in the
golden zebrafish restored wild-type pigmentation. European populations
carry a slightly different version of the slc24A5 gene than do African and
East Asian populations. A genetic polymorphism that changes one amino acid
in the coding region of the gene correlates with skin pigmentation levels,
which suggests that slc24A5 may contribute to skin color in humans.


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Hiding in the Long Grass
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Since the seminal work of MacArthur and Wilson on the theory of island
biogeography, studies on this topic have focused mainly on the relation of
species richness with island parameters such as area, distance, and habitat
variability. The population biology of individual species in the island
context has received much less attention. Schoener et al. (p. 1807; see the
Perspective by Thorpe) report results from an experiment using Anolis
lizards and an introduced lizard predator on small islands in the Bahamas
archipelago. In the absence of the predator, there was a highly regular
(decreasing) correlation of lizard survival to a key habitat variable
(vegetation height). In the presence of the predator, the situation was
nearly reversed, such that prey survival was highest in the tallest
vegetation.

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Modification of Electrical Synapses
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The brain has two main types of synapses, chemical and electrical.
Electrical synapses represent a major form of communication between
interneurons in the mammalian nervous system. They play an important role
in synchronization of activity in local cell populations because their
speed and reliability allows signals to spread across whole networks at a
time scale that is sufficient to preserve precise timing of signals between
distant neurons. In spite of these potentially vital functions, electrical
synapses have generally been regarded as stereotypic and nonflexible.
However, Landisman and Connors (p. 1809) found that transmission across
electrical synapses can undergo long-term modifications just like chemical
synapses. The modulation depends on activation of metabotropic glutamate
receptors, which presumably trigger intracellular signal cascades
modulating the connexins that constitute the electrical synapses.

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Snails on the Rampage
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There has been unprecedented and massive die-off of southeastern United
States salt marshes during the past 5 years, with potentially serious
consequences for coastal protection and integrity. Silliman et al. (p.
1803) surveyed more than 1200 kilometers of coastline and found
high-density fronts of plant-grazing snails (~1500 individuals per square
meter) mowing down marsh plants at 11 of 12 die-off sites. Die-off was
initiated by drought-induced stress. Snail fronts developed at the edges of
the die-off zones, and then spread across remaining healthy areas. These
interactions between climatic and trophic factors may lead to further
degradation or even collapse of these ecologically and economically
important systems.

CREDIT: SILLIMAN ET AL.

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Inhibiting Brain Repair
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Neuronal axons in the mammalian central and peripheral nervous system are
generally ensheathed in myelin that is generated by nonneuronal cells. In
response to injury in the peripheral nervous system, new axons can sprout
from unmyelinated gaps called the Nodes of Ranvier, but this response
rarely occurs in the central nervous system (CNS). Huang et al. (p. 1813,
published online 17 November) have identified a precursor oligodendrocyte
cell type whose processes envelope nodes in the CNS and inhibit axon
sprouting. The processes express a glycoprotein previously thought
exclusive to compact myelin. Mice lacking the glycoprotein exhibited
abnormal node formation and nodal axon sprouting. Overcoming the inhibitory
nature of these cells may be clinically important in recovery from injury.

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MicroRNA Management of the Genome
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MicroRNAs (miRNAs), small, ~22-nucleotide noncoding RNAs that have been
found in most of the plants and animals so far studied, generally regulate
gene expression by suppressing the activity of messenger RNAs (mRNA)
bearing complementary target sequences. These targets, or "seeds," are
apparently only seven to eight nucleotides long, and so, all things being
equal, should occur randomly throughout the genome with relatively high
frequency. Farh et al. (p. 1817, published online 24 November) now show
that all things are not equal: Expression of regulated seed-bearing mRNAs
correlates with the presence of the appropriate miRNA. However,
nonregulated mRNAs present at high levels in miRNA-expressing tissues have
a paucity of complementary seed matches in their sequence. Thus, miRNAs are
influencing the expression, the evolution, or both of the majority of
mRNAs.

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Just-in-Time Competency
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Many bacteria can take up exogenous DNA, an ability known as natural
competence. The causative agent of cholera, Vibrio cholerae, is not known
to have this property, but somehow it has clearly acquired virulence
attributes, including cholera toxin, from some other source. V. cholerae
does possess the genes used by other bacteria to assemble the necessary
machinery for DNA uptake, for example, type IV pili. Meibom et al. (p.
1824; see the Perspective by Bartlett and Azam) now show that a chitin
(which can be found in the exoskeleton of crabs, a natural host for the
bacteria) triggers V. cholerae to produce pili, and to release and exchange
functional DNA. This competency remained unnoticed in a pathogen that has
been studied for 60 years, which suggests that other noncompetent bacteria
may become so under the appropriate growth conditions.

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Looking at Glasses at Length
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At the glass transition, the viscosity of a liquid increases dramatically,
but static snapshots of the extent of ordering in these amorphous systems
(their static correlation lengths) reveal little difference. However,
numerical simulations and indirect experimental evidence indicates that as
a liquid cools, regions of correlated movements of particles become larger,
impeding the overall fluid flow, so that the length scales upon which the
material is dynamically heterogeneous appear to be increasing. Berthier et
al. (p. 1797) derive a lower bound on the four-point, time-dependent
susceptibility4(t), a general measure of dynamic correlation lengths, and
analyze data from two experimental systems--supercooled glycerol and
colloidal hard spheres--as well as simulated glass, a binary Lennard-Jones
mixture. All three systems display peaks in their appropriate dynamic
susceptibility whose height increases for slower time scales, which
indicate the presence of a growing dynamic length scale as the liquids
cool.

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Bridging the Damaged DNA Gap
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The main replicative DNA polymerase has evolved to recognize DNA with high
fidelity, but this capability also makes it very poor at dealing with
damaged DNA, where it very often stalls at the point of damage. A series of
"damage-specific" DNA polymerases that can handle distorted or abasic
templates are recruited to the stalled polymerase partly through the
ubiquitinylation of proliferating cell nuclear antigen (PCNA)--but how this
occurs has been a mystery. Bienko et al. (p. 1821) now show that all the
Y-family damage-specific translesion synthesis (TLS) polymerases contain
two previously undetected types of ubiquitin binding domain. Colocalization
of two TLS polymerases with PCNA in replication factories depends on these
ubiquitin binding domains, as do the ability to interact with
ubiquitinylated-PCNA and the ability to facilitate DNA repair.

_______________________________________________________________________
Copyright © 2005 by the American Association for the Advancement of
Science.

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